Mediators of Inflammation The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. The Roles of CD147 and/or Cyclophilin A in Kidney Diseases Wed, 17 Dec 2014 07:42:37 +0000 CD147 is a widely expressed integral plasma membrane glycoprotein and has been involved in a variety of physiological and pathological activities in combination with different partners, including cyclophilins, caveolin-1, monocarboxylate transporters, and integrins. Recent data demonstrate that both CyPA and CD147 significantly contribute to renal inflammation, acute kidney injury, renal fibrosis, and renal cell carcinoma. Here we review the current understanding of cyclophilin A and CD147 expression and functions in kidney diseases and potential implications for treatment of kidney diseases. Xin Qu, Chunting Wang, Jicheng Zhang, Guoqiang Qie, and Jianxin Zhou Copyright © 2014 Xin Qu et al. All rights reserved. On the Significance of New Biochemical Markers for the Diagnosis of Premature Labour Mon, 08 Dec 2014 13:09:43 +0000 Preterm labour is defined as a birth taking place between 22nd and 37th weeks of gestation. Despite numerous studies on the aetiology and pathogenesis of preterm labour, its very cause still remains unclear. The importance of the cytokines and acute inflammation in preterm labour aetiology is nowadays well-proven. However, chronic inflammation as an element of the pathogenesis of premature labour is still unclear. This paper presents a literature review on the damage-associated molecular patterns (DAMPs), receptors for advanced glycation end products (RAGE), negative soluble isoforms of RAGE, chemokine-stromal cell-derived factor-1 (SDF-1) and one of the adipokines, resistin, in the pathogenesis of preterm labour. We conclude that the chronic inflammatory response can play a much more important role in the pathogenesis of preterm delivery than the acute one. Rafał Rzepka, Barbara Dołęgowska, Aleksandra Rajewska, and Sebastian Kwiatkowski Copyright © 2014 Rafał Rzepka et al. All rights reserved. Elevated Serum IgG4 Defines Specific Clinical Phenotype of Rheumatoid Arthritis Sun, 07 Dec 2014 12:37:05 +0000 Objectives. To explore the correlation of serum IgG4 (sIgG4) with clinical manifestations or therapeutic response in rheumatoid arthritis (RA). Methods. Consecutive 136 RA patients were recruited and followed up at regular interval. SIgG4 was detected by immunonephelometry. Serial synovial tissue sections from 46 RA patients were stained immunohistochemically for IgG4. Results. Forty-six percent of 136 RA patients had elevated sIgG4. Patients with elevated sIgG4 had higher sIgG4/sIgG ratio, C-reactive protein, erythrocyte sedimentation rate, rheumatoid factor, and anticyclic citrullinated peptide antibodies than those with normal sIgG4 (all ). Among 45 patients who received methotrexate and leflunomide therapy, 50% (9/18) of patients with elevated sIgG4 and 85% (23/27) of patients with normal sIgG4 reached therapeutic target (disease activity score of 28 joints < 3.2) at 6-month visit (, ). IgG4-positive plasma cell count correlated positively with sIgG4, total synovitis score, and CD3-, CD20-, and CD38-positive cell counts (all ). Conclusions. Our results showed that elevated sIgG4 in RA is common and disproportional to total IgG and RA with elevated sIgG4 may be a specific clinical phenotype with higher disease activity, higher level of autoantibodies, and poor response to methotrexate and leflunomide therapy. Le-Feng Chen, Ying-Qian Mo, Jian-Da Ma, Ling Luo, Dong-hui Zheng, and Lie Dai Copyright © 2014 Le-Feng Chen et al. All rights reserved. Effect of Proinflammatory Cytokines (IL-6, TNF-α, and IL-1β) on Clinical Manifestations in Indian SLE Patients Sun, 07 Dec 2014 07:22:43 +0000 Systemic lupus erythematosus (SLE) is an inflammatory rheumatic disease characterized by production of autoantibodies and organ damage. Elevated levels of cytokines have been reported in SLE patients. In this study we have investigated the effect of proinflammatory cytokines (IL-6, TNF-α, and IL-1β) on clinical manifestations in 145 Indian SLE patients. One hundred and forty-five healthy controls of the same ethnicity served as a control group. Clinical disease activity was scored according to SLEDAI score. Accordingly, 110 patients had active disease and 35 patients had inactive disease. Mean levels of IL-6, TNF-α, and IL-1β were found to be significantly higher in SLE patients than healthy controls (). Mean level of IL-6 for patients with active disease ( pg/mL) was significantly higher () than those of inactive disease patients ( pg/mL). Mean level of TNF-α was  pg/mL for patients with active disease while it was  pg/mL for those with inactive disease and this difference was statistically significant (). Similar results were obtained for IL-1β (). Correlation between IL-6, TNF-α, and IL-1β serum levels and SLEDAI score was observed (, , and , resp.). This study supports the role of these proinflammatory cytokines as inflammatory mediators in active stage of disease. Vinod Umare, Vandana Pradhan, Milind Nadkar, Anjali Rajadhyaksha, Manisha Patwardhan, Kanjaksha K. Ghosh, and Anita H. Nadkarni Copyright © 2014 Vinod Umare et al. All rights reserved. Control and Resolution Mechanisms of the Inflammatory Response Mon, 01 Dec 2014 06:06:33 +0000 Víctor M. Baizabal-Aguirre, Carlos Rosales, Constantino López-Macías, and Marisa I. Gómez Copyright © 2014 Víctor M. Baizabal-Aguirre et al. All rights reserved. Collaborative Action of Toll-Like and Nod-Like Receptors as Modulators of the Inflammatory Response to Pathogenic Bacteria Mon, 01 Dec 2014 00:10:13 +0000 Early sensing of pathogenic bacteria by the host immune system is important to develop effective mechanisms to kill the invader. Microbial recognition, activation of signaling pathways, and effector mechanisms are sequential events that must be highly controlled to successfully eliminate the pathogen. Host recognizes pathogens through pattern-recognition receptors (PRRs) that sense pathogen-associated molecular patterns (PAMPs). Some of these PRRs include Toll-like receptors (TLRs), nucleotide-binding oligomerization domain-like receptors (NLRs), retinoic acid-inducible gene-I- (RIG-I-) like receptors (RLRs), and C-type lectin receptors (CLRs). TLRs and NLRs are PRRs that play a key role in recognition of extracellular and intracellular bacteria and control the inflammatory response. The activation of TLRs and NLRs by their respective ligands activates downstream signaling pathways that converge on activation of transcription factors, such as nuclear factor-kappaB (NF-κB), activator protein-1 (AP-1) or interferon regulatory factors (IRFs), leading to expression of inflammatory cytokines and antimicrobial molecules. The goal of this review is to discuss how the TLRs and NRLs signaling pathways collaborate in a cooperative or synergistic manner to counteract the infectious agents. A deep knowledge of the biochemical events initiated by each of these receptors will undoubtedly have a high impact in the design of more effective strategies to control inflammation. Javier Oviedo-Boyso, Alejandro Bravo-Patiño, and Víctor M. Baizabal-Aguirre Copyright © 2014 Javier Oviedo-Boyso et al. All rights reserved. Control of the Inflammatory Response Mechanisms Mediated by Natural and Induced Regulatory T-Cells in HCV-, HTLV-1-, and EBV-Associated Cancers Sun, 30 Nov 2014 12:35:26 +0000 Virus infections are involved in chronic inflammation and, in some cases, cancer development. Although a viral infection activates the immune system’s response that eradicates the pathogen mainly through inflammatory mechanisms, it is now recognized that this inflammatory condition is also favorable to the development of tumors. Indeed, it is well described that viruses, such as hepatitis C virus (HCV), Epstein Barr virus (EBV), human papillomavirus (HPV) or human T-cell lymphotropic virus type-1 (HTLV-1), are important risk factors for tumor malignancies. The inflammatory response is a fundamental immune mechanism which involves several molecular and cellular components consisting of cytokines and chemokines that are released by various proinflammatory cells. In parallel to this process, some endogenous recruited components release anti-inflammatory mediators to restore homeostasis. The development of tools and strategies using viruses to hijack the immune response is mostly linked to the presence of regulatory T-cells (Treg) that can inhibit inflammation and antiviral responses of other effector cells. In this review, we will focus on current understanding of the role of natural and induced Treg in the control and the resolution of inflammatory response in HCV-, HTLV-1-, and EBV-associated cancers. Laurissa Ouaguia, Dhafer Mrizak, Sarah Renaud, Olivier Moralès, and Nadira Delhem Copyright © 2014 Laurissa Ouaguia et al. All rights reserved. Immunomodulatory Effects of Polysaccharide from Marine Fungus Phoma herbarum YS4108 on T Cells and Dendritic Cells Sun, 30 Nov 2014 07:16:31 +0000 YCP, as a kind of natural polysaccharides from the mycelium of marine filamentous fungus Phoma herbarum YS4108, has great antitumor potential via enhancement of host immune response, but little is known about the molecular mechanisms. In the present study, we mainly focused on the effects and mechanisms of YCP on the specific immunity mediated by dendritic cells (DCs) and T cells. T cell /DC activation-related factors including interferon- (IFN-) γ, interleukin-12 (IL-12), and IL-4 were examined with ELISA. Receptor knock-out mice and fluorescence-activated cell sorting are used to analyze the YCP-binding receptor of T cells and DCs. RT-PCR is utilized to measure MAGE-A3 for analyzing the tumor-specific killing effect. In our study, we demonstrated YCP can provide the second signal for T cell activation, proliferation, and IFN-γ production through binding to toll-like receptor- (TLR-) 2 and TLR-4. YCP could effectively promote IL-12 secretion and expression of markers (CD80, CD86, and MHC II) via TLR-4 on DCs. Antigen-specific immunity against mouse melanoma cells was strengthened through the activation of T cells and the enhancement of capacity of DCs by YCP. The data supported that YCP can exhibit specific immunomodulatory capacity mediated by T cells and DCs. Song Chen, Ran Ding, Yan Zhou, Xian Zhang, Rui Zhu, and Xiang-Dong Gao Copyright © 2014 Song Chen et al. All rights reserved. GSK-3β Inhibition Attenuates CLP-Induced Liver Injury by Reducing Inflammation and Hepatic Cell Apoptosis Sun, 30 Nov 2014 06:23:02 +0000 Liver dysfunction has been known to occur frequently in cases of sepsis. Excessive inflammation and apoptosis are pathological features of acute liver failure. Recent studies suggest that activation of glycogen synthase kinase- (GSK-) 3β is involved in inflammation and apoptosis. We aimed to investigate the protective effects of GSK-3β inhibition on polymicrobial sepsis-induced liver injury and to explore the possible mechanisms. Polymicrobial sepsis was induced by cecal ligation and puncture (CLP), and SB216763 was used to inhibit GSK-3β in C57BL/6 mice. GSK-3β was activated following CLP. Administration of SB216763 decreased mortality, ameliorated liver injury, and reduced hepatic apoptosis. The inhibition of GSK-3β also reduced leukocyte infiltration and hepatic inflammatory cytokine expression and release. Moreover, GSK-3β inhibition suppressed the transcriptional activity of nuclear factor-kappa B (NF-κB) but enhanced the transcriptional activity of cAMP response element binding protein (CREB) in the liver. In in vitro studies, GSK-3β inhibition reduced inflammatory cytokine production via modulation of NF-κB and CREB signaling pathways in lipopolysaccharide-stimulated macrophages. In conclusion, these findings suggest that GSK-3β blockade protects against CLP-induced liver via inhibition of inflammation by modulating NF-κB and CREB activity and suppression of hepatic apoptosis. Hui Zhang, Wenjie Wang, Haoshu Fang, Yan Yang, Xiaolan Li, Junli He, Xiaojing Jiang, Weipeng Wang, Shenpei Liu, Jifa Hu, Anding Liu, Uta Dahmen, and Olaf Dirsch Copyright © 2014 Hui Zhang et al. All rights reserved. Clinical Significance of IL-23 Regulating IL-17A and/or IL-17F Positive Th17 Cells in Chronic Periodontitis Sun, 30 Nov 2014 00:10:29 +0000 Objective. To investigate the expression level and clinical significance of (IL-17A+ and/or IL-17F+) Th17 cells under IL-23 regulation in patients of chronic periodontitis (CP) and healthy controls (HC). Materials and Methods. The whole peripheral blood samples were collected from 30 CP patients and 25 healthy controls. Flow cytometry was used to test the (IL-17A+ and/or IL-17F+) Th17 expression level. Recombinant human IL-23 (rhIL-23) was used to detect Th17 differentiation and expansion. Correlation coefficient analysis between Th17 expression level and clinical parameters was analyzed by SPSS software. Results. Flow cytometry results showed that IL-17A+IL-17F− and IL-17A−IL-17F+ Th17 were both increased in CP group than in HC group (P < 0.01), while, under recombinant human IL-23 (rhIL-23) stimulation, the number of IL-17A+IL-17F− Th17 cells was significantly increased in both CP and HC groups (P < 0.01). Interestingly, IL-17A−IL-17F+ Th17 cells were only increased in CP group after rhIL-23 stimulation. Additionally, correlation coefficient analysis showed significant correlation between IL-17A+IL-17F− Th17 cell and attachment loss or probing depth (P < 0.05). Conclusions. This study indicates that both the IL-17A+IL-17F− and IL-17A−IL-17F+ Th17 cells may be involved in pathogenesis of periodontitis. The role of these Th17 cells in the disease pathogenesis needs to be further investigated. Zhenhua Luo, Hui Wang, Yunlong Wu, Zheng Sun, and Yafei Wu Copyright © 2014 Zhenhua Luo et al. All rights reserved. Anabolic Properties of High Mobility Group Box Protein-1 in Human Periodontal Ligament Cells In Vitro Thu, 27 Nov 2014 08:49:30 +0000 High mobility group box protein-1 (HMGB1) is mainly recognized as a chemoattractant for macrophages in the initial phase of host response to pathogenic stimuli. However, recent findings provide evidence for anabolic properties in terms of enhanced proliferation, migration, and support of wound healing capacity of mesenchymal cells suggesting a dual role of the cytokine in the regulation of immune response and subsequent regenerative processes. Here, we examined potential anabolic effects of HMGB1 on human periodontal ligament (PDL) cells in the regulation of periodontal remodelling, for example, during orthodontic tooth movement. Preconfluent human PDL cells (hPDL) were exposed to HMGB1 protein and the influence on proliferation, migration, osteogenic differentiation, and biomineralization was determined by MTS assay, real time PCR, immunofluorescence cytochemistry, ELISA, and von Kossa staining. HMGB1 protein increased hPDL cell proliferation, migration, osteoblastic marker gene expression, and protein production as well as mineralized nodule formation significantly. The present findings support the dual character of HMGB1 with anabolic therapeutic potential that might support the reestablishment of the structural and functional integrity of the periodontium following periodontal trauma such as orthodontic tooth movement. Michael Wolf, Stefan Lossdörfer, Piero Römer, Rogerio Bastos Craveiro, James Deschner, and Andreas Jäger Copyright © 2014 Michael Wolf et al. All rights reserved. Serum Amyloid A as a Marker of Persistent Inflammation and an Indicator of Cardiovascular and Renal Involvement in Patients with Rheumatoid Arthritis Thu, 27 Nov 2014 06:16:21 +0000 Objectives. Rheumatoid arthritis (RA) is a systemic, inflammatory disease. Serum amyloid A (SAA) is an acute-phase protein, involved in pathogenesis of atherosclerosis. The aim of the study was to assess serum concentration of SAA in RA patients, with reference to other inflammatory parameters and markers of extra-articular involvement. Methods. The study population consisted of 140 RA patients, low/moderate disease activity (L/MDA) in 98 (70%) patients and high disease activity (HDA) in 42 (30%). Comprehensive clinical and laboratory assessment was performed with evaluation of electrocardiogram and carotid intima-media thickness. Results. The mean SAA concentration [327.0 (263.4) mg/L] was increased highly above the normal value, even in patients with L/MDA. Simultaneously, SAA was significantly higher in patients with HDA versus L/MDA. The mean SAA concentration was significantly higher in patients treated with glucocorticoids, was inversely associated with QTc duration, and was markedly higher in patients with atherosclerotic plaques, emphasizing increased CV risk. SAA was significantly higher in patients with increased cystatin-C level. Conclusions. In RA patients, high serum SAA concentration was strongly associated with activity of the disease and risk of CV and renal involvement. Recurrent assessment of SAA may facilitate searching patients with persistent inflammation and risk of extra-articular complications. Bożena Targońska-Stępniak and Maria Majdan Copyright © 2014 Bożena Targońska-Stępniak and Maria Majdan. All rights reserved. CD206+ Cell Number Differentiates Influenza A (H1N1)pdm09 from Seasonal Influenza A Virus in Fatal Cases Tue, 25 Nov 2014 13:11:30 +0000 In 2009, a new influenza A (H1N1) virus affected many persons around the world. There is an urgent need for finding biomarkers to distinguish between influenza A (H1N1)pdm09 and seasonal influenza virus. We investigated these possible biomarkers in the lung of fatal cases of confirmed influenza A (H1N1)pdm09. Cytokines (inflammatory and anti-inflammatory) and cellular markers (macrophages and lymphocytes subpopulation markers) were analyzed in lung tissue from both influenza A (H1N1)pdm09 and seasonal influenza virus. High levels of IL-17, IFN-γ, and TNF-α positive cells were identical in lung tissue from the influenza A (H1N1)pdm09 and seasonal cases when compared with healthy lung tissue (). Increased IL-4+ cells, and CD4+ and CD14+ cells were also found in high levels in both influenza A (H1N1)pdm09 and seasonal influenza virus (). Low levels of CD206+ cells (marker of alternatively activated macrophages marker in lung) were found in influenza A (H1N1)pdm09 when compared with seasonal influenza virus (), and the ratio of CD206/CD14+ cells was 2.5-fold higher in seasonal and noninfluenza group compared with influenza A (H1N1)pdm09 (). In conclusion, CD206+ cells differentiate between influenza A (H1N1)pdm09 and seasonal influenza virus in lung tissue of fatal cases. Heidi G. Rodriguez-Ramirez, Mario C. Salinas-Carmona, Oralia Barboza-Quintana, Americo Melo-de la Garza, Luis Angel Ceceñas-Falcon, Lilia M. Rangel-Martinez, and Adrian G. Rosas-Taraco Copyright © 2014 Heidi G. Rodriguez-Ramirez et al. All rights reserved. Osteopontin Expression in the Brain Triggers Localized Inflammation and Cell Death When Immune Cells Are Activated by Pertussis Toxin Mon, 24 Nov 2014 09:22:55 +0000 Upregulation of osteopontin (OPN) is a characteristic of central nervous system pathologies. However, the role of OPN in inflammation is still controversial, since it can both prevent cell death and induce the migration of potentially damaging inflammatory cells. To understand the role of OPN in inflammation and cell survival, we expressed OPN, utilizing an adenoviral vector, in the caudoputamen of mice deficient in OPN, using beta-galactosidase- (β-gal-) expressing vector as control. The tissue pathology and the expression of proinflammatory genes were compared in both treatments. Interestingly, inflammatory infiltrate was only found when the OPN-vector was combined with a peripheral treatment with pertussis toxin (Ptx), which activated peripheral cells to express the OPN receptor CD44v6. Relative to β-gal, OPN increased the levels of inflammatory markers, including IL13Rα1, CXCR3, and CD40L. In Ptx-treated OPN KOs, apoptotic TUNEL+ cells surrounding the OPN expression site increased, compared to β-gal. Together, these results show that local OPN expression combined with a peripheral inflammatory stimulus, such as Ptx, may be implicated in the development of brain inflammation and induction of cell death, by driving a molecular pattern characteristic of cytotoxicity. These are characteristics of inflammatory pathologies of the CNS in which OPN upregulation is a hallmark. Maria Cecilia Garibaldi Marcondes, Ryan Ojakian, Nikki Bortell, Claudia Flynn, Bruno Conti, and Howard S. Fox Copyright © 2014 Maria Cecilia Garibaldi Marcondes et al. All rights reserved. Prognostic Value of Plasma Pentraxin-3 Levels in Patients with Stable Coronary Artery Disease after Drug-Eluting Stent Implantation Mon, 24 Nov 2014 06:19:23 +0000 Pentraxin-3 (PTX3) is an inflammatory marker thought to be more specific to cardiovascular inflammation than C-reactive protein (CRP). Our aim was to assess the prognostic value of PTX3 in patients with stable coronary artery disease (CAD) after drug eluting stent (DES) implantation. Plasma PTX3 levels were measured before percutaneous coronary intervention (PCI) and at 24 h post-PCI in 596 consecutive patients with stable CAD. Patients were followed up for a median of 3 years (range 1–5) for major adverse cardiovascular events (MACEs). We found that the post-PCI plasma PTX3 levels were significantly higher at 24 h after PCI than pre-PCI, patients with MACEs had higher post-PCI PTX3 levels compared with MACEs-free patients, patients with higher post-PCI PTX3 levels (median > 4.384 ng/mL) had a higher risk for MACEs than those with PTX3 < 4.384 ng/mL, and post-PCI PTX3, cTnI, multiple stents, and age but not high-sensitivity CRP (hsCRP) were independently associated with the prevalence of MACEs after DES implantation. The present study shows that post-PCI PTX3 may be a more reliable inflammatory predictor of long-term MACEs in patients with stable CAD undergoing DES implantation than CRP. Measurement of post-PCI PTX3 levels could provide a rationale for risk stratification of patients with stable CAD after DES implantation. Liu Haibo, Guo Xiaofang, Wang Chunming, Yuan Jie, Chen Guozhong, Zhang Limei, Cao Yong, Fang Yu, Bao Yingchun, Yu Wangjun, and Ge Junbo Copyright © 2014 Liu Haibo et al. All rights reserved. Mushrooms: A Potential Natural Source of Anti-Inflammatory Compounds for Medical Applications Sun, 23 Nov 2014 00:00:00 +0000 For centuries, macrofungi have been used as food and medicine in different parts of the world. This is mainly attributed to their nutritional value as a potential source of carbohydrates, proteins, amino acids, and minerals. In addition, they also include many bioactive metabolites which make mushrooms and truffles common components in folk medicine, especially in Africa, the Middle East, China, and Japan. The reported medicinal effects of mushrooms include anti-inflammatory effects, with anti-inflammatory compounds of mushrooms comprising a highly diversified group in terms of their chemical structure. They include polysaccharides, terpenoids, phenolic compounds, and many other low molecular weight molecules. The aims of this review are to report the different types of bioactive metabolites and their relevant producers, as well as the different mechanisms of action of mushroom compounds as potent anti-inflammatory agents. Elsayed A. Elsayed, Hesham El Enshasy, Mohammad A. M. Wadaan, and Ramlan Aziz Copyright © 2014 Elsayed A. Elsayed et al. All rights reserved. IL-1β and TNFα Promote Monocyte Viability through the Induction of GM-CSF Expression by Rheumatoid Arthritis Synovial Fibroblasts Mon, 17 Nov 2014 13:36:17 +0000 Background. Macrophages and synovial fibroblasts (SF) are two major cells implicated in the pathogenesis of rheumatoid arthritis (RA). SF could be a source of cytokines and growth factors driving macrophages survival and activation. Here, we studied the effect of SF on monocyte viability and phenotype. Methods. SF were isolated from synovial tissue of RA patients and CD14+ cells were isolated from peripheral blood of healthy donors. SF conditioned media were collected after 24 hours of culture with or without stimulation with TNFα or IL-1β. Macrophages polarisation was studied by flow cytometry. Results. Conditioned medium from SF significantly increased monocytes viability by 60% compared to CD14+ cells cultured in medium alone . This effect was enhanced using conditioned media from IL-1β and TNFα stimulated SF. GM-CSF but not M-CSF nor IL34 blocking antibodies was able to significantly decrease monocyte viability by 30% when added to the conditioned media from IL-1β and TNFα stimulated SF . Finally, monocyte cultured in presence of SF conditioned media did not exhibit a specific M1 or M2 phenotype. Conclusion. Overall, rheumatoid arthritis synovial fibroblasts stimulated with proinflammatory cytokines (IL-1β and TNFα) promote monocyte viability via GM-CSF but do not induce a specific macrophage polarization. Christelle Darrieutort-Laffite, Marie-Astrid Boutet, Mathias Chatelais, Régis Brion, Frédéric Blanchard, Dominique Heymann, and Benoit Le Goff Copyright © 2014 Christelle Darrieutort-Laffite et al. All rights reserved. Paraoxonase1 Genetic Polymorphisms in a Mixed Ancestry African Population Sun, 16 Nov 2014 06:43:07 +0000 Paraoxonase 1 (PON1) activity is markedly influenced by coding polymorphisms, Q/R at position 192 and M/L at position 55 of the PON1 gene. We investigated the frequencies of these polymorphisms and their effects on PON1 and antioxidant activities in 844 South African mixed ancestry individuals. Genotyping was done using allele-specific TaqMan technology, PON1 activities were measured using paraoxon and phenylacetate, oxidative status was determined by measuring the antioxidant activities of ferric reducing antioxidant power and trolox equivalent antioxidant capacity, and lipid peroxidation markers included malondialdehyde and oxidized LDL. The frequencies of Q192R and L55M were 47.6% and 28.8%, respectively, and the most common corresponding alleles were 192R (60.4%) and 55M (82.6%). The Q192 was significantly associated with 5.8 units’ increase in PON1 concentration and 15.4 units’ decrease in PONase activity after adjustment for age, sex, BMI, and diabetes, with suggestion of differential effects by diabetes status. The PON1 L55 variant was associated with none of the measured indices. In conclusion, we have shown that the Q192R polymorphism is a determinant of both PON1 concentration and activity and this association appeared to be enhanced in subjects with diabetes. M. Macharia, A. P. Kengne, D. M. Blackhurst, R. T. Erasmus, and T. E. Matsha Copyright © 2014 M. Macharia et al. All rights reserved. Excessive Refined Carbohydrates and Scarce Micronutrients Intakes Increase Inflammatory Mediators and Insulin Resistance in Prepubertal and Pubertal Obese Children Independently of Obesity Sun, 16 Nov 2014 06:42:25 +0000 Background. Low-grade inflammation is the link between obesity and insulin resistance. Because physiologic insulin resistance occurs at puberty, obese pubertal children are at higher risk for insulin resistance. Excessive diets in refined carbohydrates and saturated fats are risk factors for insulin resistance, but calcium, magnesium, vitamin-D, and the omega-3 fatty acids likely protect against inflammation and insulin resistance. Objective. To analyze interactions among dietary saturated fat, refined carbohydrates, calcium, magnesium, vitamin D, and omega-3 fatty acids on the risk of inflammation and insulin resistance in a sample of prepubertal and pubertal children. Methods. A sample of 229 children from Mexico City was analyzed in a cross-sectional design. Anthropometric measurements, 24 h recall questionnaires, and blood samples were obtained. Serum insulin, glucose, calcium, magnesium, 25-OHD3, C-reactive protein, leptin, adiponectin, and erythrocytes fatty acids were measured. Parametric and nonparametric statistics were used for analysis. Results. While mean macronutrients intake was excessive, micronutrients intake was deficient . Inflammation determinants were central obesity and magnesium-deficient diets. Determinants of insulin resistance were carbohydrates intake and circulating magnesium and adiponectin. Conclusions. Magnesium-deficient diets are determinants of inflammation, while high intake of refined carbohydrates is a risk factor for insulin resistance, independently of central adiposity. Mardia López-Alarcón, Otilia Perichart-Perera, Samuel Flores-Huerta, Patricia Inda-Icaza, Maricela Rodríguez-Cruz, Andrea Armenta-Álvarez, María Teresa Bram-Falcón, and Marielle Mayorga-Ochoa Copyright © 2014 Mardia López-Alarcón et al. All rights reserved. Maternal Plasma and Amniotic Fluid Chemokines Screening in Fetal Down Syndrome Sun, 16 Nov 2014 00:00:00 +0000 Objective. Chemokines exert different inflammatory responses which can potentially be related to certain fetal chromosomal abnormalities. The aim of the study was to determine the concentration of selected chemokines in plasma and amniotic fluid of women with fetal Down syndrome. Method. Out of 171 amniocentesis, we had 7 patients with confirmed fetal Down syndrome (15th–18th weeks of gestation). For the purpose of our control, we chose 14 women without confirmed chromosomal aberration. To assess the concentration of chemokines in the blood plasma and amniotic fluid, we used a protein macroarray, which allows the simultaneous determination of 40 chemokines per sample. Results. We showed significant decrease in the concentration of 4 chemokines, HCC-4, IL-28A, IL-31, and MCP-2, and increase in the concentration of CXCL7 (NAP-2) in plasma of women with fetal Down syndrome. Furthermore, we showed decrease in concentration of 3 chemokines, ITAC, MCP-3, MIF, and increase in concentration of 4 chemokines, IP-10, MPIF-1, CXCL7, and 6Ckine, in amniotic fluid of women with fetal Down syndrome. Conclusion. On the basis of our findings, our hypothesis is that the chemokines may play role in the pathogenesis of Down syndrome. Defining their potential as biochemical markers of Down syndrome requires further investigation on larger group of patients. Piotr Laudanski, Monika Zbucka-Kretowska, Karol Charkiewicz, Slawomir Wolczynski, Daniela Wojcik, and Radoslaw Charkiewicz Copyright © 2014 Piotr Laudanski et al. All rights reserved. Protective Effect of Baccharis trimera Extract on Acute Hepatic Injury in a Model of Inflammation Induced by Acetaminophen Wed, 12 Nov 2014 00:00:00 +0000 Background. Acetaminophen (APAP) is a commonly used analgesic and antipyretic. When administered in high doses, APAP is a clinical problem in the US and Europe, often resulting in severe liver injury and potentially acute liver failure. Studies have demonstrated that antioxidants and anti-inflammatory agents effectively protect against the acute hepatotoxicity induced by APAP overdose. Methods. The present study attempted to investigate the protective effect of B. trimera against APAP-induced hepatic damage in rats. The liver-function markers ALT and AST, biomarkers of oxidative stress, antioxidant parameters, and histopathological changes were examined. Results. The pretreatment with B. trimera attenuated serum activities of ALT and AST that were enhanced by administration of APAP. Furthermore, pretreatment with the extract decreases the activity of the enzyme SOD and increases the activity of catalase and the concentration of total glutathione. Histopathological analysis confirmed the alleviation of liver damage and reduced lesions caused by APAP. Conclusions. The hepatoprotective action of B. trimera extract may rely on its effect on reducing the oxidative stress caused by APAP-induced hepatic damage in a rat model. General Significance. These results make the extract of B. trimera a potential candidate drug capable of protecting the liver against damage caused by APAP overdose. Bruno da Cruz Pádua, Joamyr Victor Rossoni Júnior, Cíntia Lopes de Brito Magalhães, Míriam Martins Chaves, Marcelo Eustáquio Silva, Maria Lucia Pedrosa, Gustavo Henrique Bianco de Souza, Geraldo Célio Brandão, Ivanildes Vasconcelos Rodrigues, Wanderson Geraldo Lima, and Daniela Caldeira Costa Copyright © 2014 Bruno da Cruz Pádua et al. All rights reserved. Roles of 5-Lipoxygenase and Cysteinyl-Leukotriene Type 1 Receptors in the Hematological Response to Allergen Challenge and Its Prevention by Diethylcarbamazine in a Murine Model of Asthma Tue, 11 Nov 2014 13:27:52 +0000 Diethylcarbamazine (DEC), which blocks leukotriene production, abolishes the challenge-induced increase in eosinopoiesis in bone-marrow from ovalbumin- (OVA-) sensitized mice, suggesting that 5-lipoxygenase (5-LO) products contribute to the hematological responses in experimental asthma models. We explored the relationship between 5-LO, central and peripheral eosinophilia, and effectiveness of DEC, using PAS or BALB/c mice and 5-LO-deficient mutants. We quantified eosinophil numbers in freshly harvested or cultured bone-marrow, peritoneal lavage fluid, and spleen, with or without administration of leukotriene generation inhibitors (DEC and MK886) and cisteinyl-leukotriene type I receptor antagonist (montelukast). The increase in eosinophil numbers in bone-marrow, observed in sensitized/challenged wild-type mice, was abolished by MK886 and DEC pretreatment. In ALOX mutants, by contrast, there was no increase in bone-marrow eosinophil counts, nor in eosinophil production in culture, in response to sensitization/challenge. In sensitized/challenged ALOX mice, challenge-induced migration of eosinophils to the peritoneal cavity was significantly reduced relative to the wild-type PAS controls. DEC was ineffective in ALOX mice, as expected from a mechanism of action dependent on 5-LO. In BALB/c mice, challenge significantly increased spleen eosinophil numbers and DEC treatment prevented this increase. Overall, 5-LO appears as indispensable to the systemic hematological response to allergen challenge, as well as to the effectiveness of DEC. Daniela Masid-de-Brito, Túlio Queto, Maria Ignez C. Gaspar-Elsas, and Pedro Xavier-Elsas Copyright © 2014 Daniela Masid-de-Brito et al. All rights reserved. Expression of Genes Related to Prostaglandin Synthesis or Signaling in Human Subcutaneous and Omental Adipose Tissue: Depot Differences and Modulation by Adipogenesis Tue, 11 Nov 2014 13:15:01 +0000 Objectives. (1) To examine depot-specific PGE2 and PGF2α release and mRNA expression of enzymes or receptors involved in PG synthesis or signaling in human adipose tissues; (2) to identify changes in expression of these transcripts through preadipocyte differentiation; and (3) to examine associations between adipose tissue mRNA expression of these transcripts and adiposity measurements. Methods. Fat samples were obtained surgically in women. PGE2 and PGF2α release by preadipocytes and adipose tissue explants was measured. Expression levels of mRNA coding for enzymes or receptors involved in PG synthesis or signaling were measured by RT-PCR. Results. Cultured preadipocytes and explants from omental fat released more PGE2 and PGF2α than those from the subcutaneous depot and the corresponding transcripts showed consistent depot differences. Following preadipocyte differentiation, expression of PLA2G16 and PTGER3 mRNA was significantly increased whereas COX-1, COX-2, PTGIS, and PTGES mRNA abundance were decreased in both compartments ( for all). Transcripts that were stimulated during adipogenesis were those that correlated best with adiposity measurements. Conclusion. Cells from the omental fat compartment release more PGE2 and PGF2α than those from the subcutaneous depot. Obesity modulates expression of PG-synthesizing enzymes and PG receptors which likely occurs through adipogenesis-induced changes in expression of these transcripts. Andréanne Michaud, Nicolas Lacroix-Pépin, Mélissa Pelletier, Marleen Daris, Laurent Biertho, Michel A. Fortier, and André Tchernof Copyright © 2014 Andréanne Michaud et al. All rights reserved. Induction of Heme Oxygenase-1 with Hemin Reduces Obesity-Induced Adipose Tissue Inflammation via Adipose Macrophage Phenotype Switching Tue, 11 Nov 2014 08:35:05 +0000 Adipose macrophages with the anti-inflammatory M2 phenotype protect against obesity-induced inflammation and insulin resistance. Heme oxygenase-1 (HO-1), which elicits antioxidant and anti-inflammatory activity, modulates macrophage phenotypes and thus is implicated in various inflammatory diseases. Here, we demonstrate that the HO-1 inducer, hemin, protects against obesity-induced adipose inflammation by inducing macrophages to switch to the M2 phenotype. HO-1 induction by hemin reduced the production of proinflammatory cytokines (TNF-α and IL-6) from cocultured adipocytes and macrophages by inhibiting the activation of inflammatory signaling molecules (JNK and NF-κB) in both cell types. Hemin enhanced transcript levels of M2 macrophage marker genes (IL-4, Mrc1, and Clec10a) in the cocultures, while reducing transcripts of M1 macrophage markers (CD274 and TNF-α). The protective effects of hemin on adipose inflammation and macrophage phenotype switching were confirmed in mice fed a high-fat diet, and these were associated with PPARγ upregulation and STAT6 activation. These findings suggest that induction of HO-1 with hemin protects against obesity-induced adipose inflammation through M2 macrophage phenotype switching, which is induced by the PPARγ and STAT6 pathway. HO-1 inducers such as hemin may be useful for preventing obesity-induced adipose inflammation. Thai Hien Tu, Yeonsoo Joe, Hye-Seon Choi, Hun Taeg Chung, and Rina Yu Copyright © 2014 Thai Hien Tu et al. All rights reserved. Inhibition of Ocular Aldose Reductase by a New Benzofuroxane Derivative Ameliorates Rat Endotoxic Uveitis Tue, 11 Nov 2014 07:14:46 +0000 The study investigated the effects of the aldose reductase (AR) inhibitor benzofuroxane derivative 5(6)-(benzo[d]thiazol-2-ylmethoxy) benzofuroxane (herein referred to as BF-5m) on the biochemical and tissue alterations induced by endotoxic uveitis in rats. BF-5m has been administered directly into the vitreous, in order to assess the expression and levels of (i) inflammatory markers such as the ocular ubiquitin-proteasome system, NF-κB, TNF-α, and MCP-1; (ii) prooxidant and antioxidant markers such as nitrotyrosine, manganese superoxide dismutase (MnSOD), and glutathione peroxidase (GPX); (iii) apoptotic/antiapoptotic factors caspases and Bcl-xl; (iv) markers of endothelial progenitor cells (EPCs) recruitment such as CD34 and CD117. 5 μL of BF-5m (0.01; 0.05; and 0.1 μM) into the right eye decreased in a dose-dependent manner the LPS-induced inflammation of the eye, reporting a clinical score 1. It reduced the ocular levels of ubiquitin, 20S and 26S proteasome subunits, NF-κB subunits, TNF-α, MCP-1, and nitrotyrosine. BF-5m ameliorated LPS-induced decrease in levels of MnSOD and GPX. Antiapoptotic effects were seen from BF-5m by monitoring the expression of Bcl-xl, an antiapoptotic protein. Similarly, BF-5m increased recruitment of the EPCs within the eye, as evidenced by CD34 and CD117 antibodies. C. Di Filippo, M. V. Zippo, R. Maisto, M. C. Trotta, D. Siniscalco, B. Ferraro, F. Ferraraccio, C. La Motta, S. Sartini, S. Cosconati, E. Novellino, C. Gesualdo, F. Simonelli, S. Rossi, and M. D’Amico Copyright © 2014 C. Di Filippo et al. All rights reserved. 21-O-Angeloyltheasapogenol E3, a Novel Triterpenoid Saponin from the Seeds of Tea Plants, Inhibits Macrophage-Mediated Inflammatory Responses in a NF-κB-Dependent Manner Mon, 10 Nov 2014 00:00:00 +0000 21-O-Angeloyltheasapogenol E3 (ATS-E3) is a triterpenoid saponin recently isolated from the seeds of the tea tree Camellia sinensis (L.) O. Kuntze. ATS-E3 has several beneficial properties including anti-inflammatory, antidiabetic, antiatherosclerotic, and anticancer effects. Unlike other phenolic compounds isolated from tea plants, there are no studies reporting the pharmacological action of ATS-E3. In this study, we therefore aimed to explore the cellular and molecular inhibitory activities of ATS-E3 in macrophage-mediated inflammatory responses. ATS-E3 remarkably diminished cellular responses of macrophages such as FITC-dextran-induced phagocytic uptake, sodium nitroprusside- (SNP-) induced radical generation, and LPS-induced nitric oxide (NO) production. Analysis of its molecular activity showed that this compound significantly suppressed the expression of inducible NO synthase (iNOS), nuclear translocation of nuclear factor- (NF-) κB subunits (p50 and p65), phosphorylation of inhibitor of κB kinase (IKK), and the enzyme activity of AKT1. Taken together, the novel triterpenoid saponin compound ATS-E3 contributes to the beneficial effects of tea plants by exerting anti-inflammatory and antioxidative activities in an AKT/IKK/NF-κB-dependent manner. Woo Seok Yang, Jaeyoung Ko, Eunji Kim, Ji Hye Kim, Jae Gwang Park, Nak Yoon Sung, Han Gyung Kim, Sungjae Yang, Ho Sik Rho, Yong Deog Hong, Song Seok Shin, and Jae Youl Cho Copyright © 2014 Woo Seok Yang et al. All rights reserved. Effect of Low-Dose, Long-Term Roxithromycin on Airway Inflammation and Remodeling of Stable Noncystic Fibrosis Bronchiectasis Tue, 04 Nov 2014 08:25:54 +0000 Background. Noncystic fibrosis bronchiectasis (NCFB) is characterized by airway expansion and recurrent acute exacerbations. Macrolide has been shown to exhibit anti-inflammatory effects in some chronic airway diseases. Objective. To assess the efficacy of roxithromycin on airway inflammation and remodeling in patients with NCFB under steady state. Methods. The study involved an open-label design in 52 eligible Chinese patients with NCFB, who were assigned to control (receiving no treatment) and roxithromycin (receiving 150 mg/day for 6 months) groups. At baseline and 6 months, the inflammatory markers such as interleukin- (IL-)8, neutrophil elastase (NE), matrix metalloproteinase- (MMP)9, hyaluronidase (HA), and type IV collagen in sputum were measured, along with the detection of dilated bronchus by throat computed tomography scan, and assessed the exacerbation. Results. Forty-three patients completed the study. The neutrophil in the sputum was decreased in roxithromycin group compared with control . IL-8, NE, MMP-9, HA, and type IV collagen in sputum were also decreased in roxithromycin group compared with the control group (all . Airway thickness of dilated bronchus and exacerbation were reduced in roxithromycin group compared with the control (all . Conclusions. Roxithromycin can reduce airway inflammation and airway thickness of dilated bronchus in patients with NCFB. Jifeng Liu, Xiaoning Zhong, Zhiyi He, Lianghong Wei, Xiaozhen Zheng, Jianquan Zhang, Jing Bai, Wei Zhong, and Dengjun Zhong Copyright © 2014 Jifeng Liu et al. All rights reserved. Optimized “In Vitro” Culture Conditions for Human Rheumatoid Arthritis Synovial Fibroblasts Tue, 04 Nov 2014 00:00:00 +0000 The composition of synovial fluid in rheumatoid arthritis (RA) is complex and strongly influences the microenvironment of joints and it is an inseparable element of the disease. Currently, “in vitro” studies are performed on RA cells cultured in the presence of either recombinant proinflammatory cytokines-conditioned medium or medium alone. In this study, we evaluated the use of synovial fluid, derived from RA patients, as optimal culture condition to perform “in vitro” studies on RA synovial fibroblasts. We observed that synovial fluid is more effective in inducing cell proliferation with respect to TNF-alpha or culture medium alone. Spontaneous apoptosis in fibroblasts was also decreased in response to synovial fluid. The expression of proinflammatory cytokines in the presence of synovial fluid was significantly elevated with respect to cells cultured with TNF-alpha or medium, and the overall morphology of cells was also modified. In addition, modulation of intracellular calcium dynamics elicited in response to synovial fluid or TNF-alpha exposure is different and suggests a role for the purinergic signalling in the modulation of the effects. These results emphasize the importance of using RA synovial fluid in “in vitro” studies involving RA cells, in order to reproduce faithfully the physiopathological environmental characteristic of RA joints. Claudia Casnici, Donatella Lattuada, Noemi Tonna, Katia Crotta, Claudio Storini, Fabio Bianco, Marcello Claudio Truzzi, Costantino Corradini, and Ornella Marelli Copyright © 2014 Claudia Casnici et al. All rights reserved. Pentraxin 3 as a Prognostic Biomarker in Patients with Systemic Inflammation or Infection Mon, 03 Nov 2014 08:06:11 +0000 Purpose. The long pentraxin 3 (PTX3) is a key component of the humoral arm of the innate immune system. PTX3 is produced locally in response to proinflammatory stimuli. We reviewed the usefulness of systemic levels of PTX3 in critically ill patients with systemic inflammatory response syndrome (SIRS), sepsis, and bacteremia, focusing on its diagnostic and prognostic value. Methods. A PubMed search on PTX3 was conducted. The list of papers was narrowed to original studies of critically ill patients. Eleven papers on original studies of critically ill patients that report on PTX3 in SIRS, sepsis, or bacteremia were identified. Results. Systematic levels of PTX3 have little diagnostic value in critically ill patients with SIRS, sepsis, or bacteremia. Systemic levels of PTX3, however, have superior prognostic power over other commonly used biological markers in these patients. Systemic levels of PTX3 correlate positively with markers of organ dysfunction and severity-of-disease classification system scores. Finally, systemic levels of PTX3 remain elevated in the acute phase and decreased on recovery. Notably, the age of the patients and underlying disease affect systemic levels of PTX3. Conclusions. The diagnostic value of PTX3 is low in patients with sepsis. Systemic levels of PTX3 have prognostic value and may add to prognostication of patients with SIRS or sepsis, complementing severity-of-disease classification systems and other biological markers. Siguan Liu, Xin Qu, Feng Liu, and Chunting Wang Copyright © 2014 Siguan Liu et al. All rights reserved. Decreased Inflammatory Responses of Human Lung Epithelial Cells after Ethanol Exposure Are Mimicked by Ethyl Pyruvate Mon, 03 Nov 2014 00:00:00 +0000 Background and Purpose. Leukocyte migration into alveolar space plays a critical role in pulmonary inflammation resulting in lung injury. Acute ethanol (EtOH) exposure exerts anti-inflammatory effects. The clinical use of EtOH is critical due to its side effects. Here, we compared effects of EtOH and ethyl pyruvate (EtP) on neutrophil adhesion and activation of cultured alveolar epithelial cells (A549). Experimental Approach. Time course and dose-dependent release of interleukin- (IL-) 6 and IL-8 from A549 were measured after pretreatment of A549 with EtP (2.5–10 mM), sodium pyruvate (NaP, 10 mM), or EtOH (85–170 mM), and subsequent lipopolysaccharide or IL-1beta stimulation. Neutrophil adhesion to pretreated and stimulated A549 monolayers and CD54 surface expression were determined. Key Results. Treating A549 with EtOH or EtP reduced substantially the cytokine-induced release of IL-8 and IL-6. EtOH and EtP (but not NaP) reduced the adhesion of neutrophils to monolayers in a dose- and time-dependent fashion. CD54 expression on A549 decreased after EtOH or EtP treatment before IL-1beta stimulation. Conclusions and Implications. EtP reduces secretory and adhesive potential of lung epithelial cells under inflammatory conditions. These findings suggest EtP as a potential treatment alternative that mimics the anti-inflammatory effects of EtOH in early inflammatory response in lungs. B. Relja, N. Omid, K. Kontradowitz, K. Jurida, E. Oppermann, P. Störmann, I. Werner, E. Juengel, C. Seebach, and I. Marzi Copyright © 2014 B. Relja et al. All rights reserved.