ISRN Inflammation The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. Substitution of Soy Protein for Casein Prevents Oxidative Modification and Inflammatory Response Induced in Rats Fed High Fructose Diet Tue, 15 Apr 2014 00:00:00 +0000 Fructose-rich diet is known to cause metabolic dysregulation, oxidative stress, and inflammation. We aimed to compare the effects of two dietary proteins of animal and plant origins on fructose-induced oxidative stress and inflammatory changes in liver. Wistar rats were fed either starch or fructose (60%) diet with casein or soy protein (20%) as the protein source for 8 weeks. Glucose and insulin, glycated hemoglobin and fructosamine, AOPP, and FRAP were determined in circulation. Intracellular ROS, oxidatively modified proteins (4-HNE and 3-NT adducts), adiponectin, TNF-α, IL-6 and PAI-1 mRNA expression, phosphorylation and activation of JNK and IKKβ, and NF-κB binding activity were assayed in liver. In comparison with starch fed group, fructose + casein group registered significant decline in antioxidant potential and increase in plasma glucose, insulin, and glycated proteins. Increased ROS production, 4-HNE and 3-NT modified proteins, JNK and IKKβ activation, and NF-κB binding activity were observed in them along with increased gene expression of PAI-1, IL-6, and TNF-α and decreased adiponectin expression. Substitution of soy protein for casein reduced oxidative modification and inflammatory changes in fructose-fed rats. These data suggest that soy protein but not casein can avert the adverse effects elicited by chronic consumption of fructose. S. Sreeja, Rajagopalan Geetha, Emayavaramban Priyadarshini, Krishnamoorthy Bhavani, and Carani Venkatraman Anuradha Copyright © 2014 S. Sreeja et al. All rights reserved. Role of Th17 Cells in the Pathogenesis of Human IBD Tue, 25 Mar 2014 09:50:26 +0000 The gastrointestinal tract plays a central role in immune system, being able to mount efficient immune responses against pathogens, keeping the homeostasis of the human gut. However, conditions like Crohn’s disease (CD) or ulcerative colitis (UC), the main forms of inflammatory bowel diseases (IBD), are related to an excessive and uncontrolled immune response against normal microbiota, through the activation of CD4+ T helper (Th) cells. Classically, IBD was thought to be primarily mediated by Th1 cells in CD or Th2 cells in UC, but it is now known that Th17 cells and their related cytokines are crucial mediators in both conditions. Th17 cells massively infiltrate the inflamed intestine of IBD patients, where they produce interleukin- (IL-) 17A and other cytokines, triggering and amplifying the inflammatory process. However, these cells show functional plasticity, and they can be converted into either IFN-γ producing Th1 cells or regulatory T cells. This review will summarize the current knowledge regarding the regulation and functional role of Th17 cells in the gut. Deeper insights into their plasticity in inflammatory conditions will contribute to advancing our understanding of the mechanisms that regulate mucosal homeostasis and inflammation in the gut, promoting the design of novel therapeutic approaches for IBD. Julio Gálvez Copyright © 2014 Julio Gálvez. All rights reserved. The Value of Admission Serum IL-8 Monitoring and the Correlation with IL-8 (-251A/T) Polymorphism in Critically Ill Patients Thu, 06 Mar 2014 08:01:03 +0000 Background. The clinical management of sepsis is a highly complicated process. Disruption of the immune system explains in part the major variation in sepsis outcome. IL-8 is a proinflammatory cytokine, genetic polymorphism of this cytokine could explain the outcome of sepsis. The present study was conducted to determine the value of serum IL-8 monitoring and its (-251A/T) genetic polymorphism in critically ill patients. Patients and Methods. 180 critically ill patients were allocated into two groups, 90 septic patients (sepsis group) and 90 nonseptic patients (SIRS group). Admission serum IL-8 and its (-251A/T) mutant allele were detected. Results. The admission mean value of serum IL-8 was significantly elevated in sepsis group. In both groups, the mean value of serum IL-8 in nonsurvived patients and patients with IL-8 (-251A/T) mutant allele was significantly higher. A positive correlation of survival and IL-8 (-251A/T) mutant allele was detected in both groups. The serum IL-8 distinguished wild from IL-8 (-251A/T) mutant allele at a cut-off value of 600 pg/mL. Conclusion. The admission mean value of serum IL-8 was significantly elevated in septic, nonsurvived, and patients with IL-8 (-251A/T) mutant alleles. A positive correlation of survival and IL-8 (-251A/T) mutant allele patients was detected. Ayman Abd Al-Maksoud Yousef, Ghada Abdulmomen Suliman, and Maaly Mohamed Mabrouk Copyright © 2014 Ayman Abd Al-Maksoud Yousef et al. All rights reserved. Scientific Validation of Gentiana kurroo Royle for Anti-Inflammatory and Immunomodulatory Potential Sun, 23 Feb 2014 09:38:49 +0000 Gentiana kurroo Royle is a critically endangered medicinal plant species endemic to the northwestern Himalayas. This plant was studied for the immunomodulatory and anti-inflammatory potential. Carrageenan paw edema model was used to study the potential of the drug in inflammation in Wistar rats. SRBC specific haemagglutination titre and DTH assays were carried out in Balb/C mice for observing the effect of test drugs on immune system. The plant extracts were found to be active against inflammation. The methanolic fraction was observed to be the most effective in inhibition of paw edema with the inhibitory potential of 47.62%. In immunomodulation studies the plant extracts showed the immunosuppressant activity. Methanolic fraction was observed to have maximum potential for the suppression of both humoral (57.57% and 54.05%) and cell mediated immunity (65.27% and 75%). From these studies, it can be concluded that the extracts of plant are having anti-inflammatory and immunosuppressant activity. Since in chronic inflammation like arthritis there is the involvement of immune system, this plant may serve as an alternative for the treatment of autoimmune diseases like arthritis. Khan Mubashir, Khalid Ghazanfar, Bashir A. Ganai, Seema Akbar, Akhtar H. Malik, and Akbar Masood Copyright © 2014 Khan Mubashir et al. All rights reserved. Antioedematous and Analgesic Properties of Fertile Fronds of Drynaria quercifolia Mon, 20 Jan 2014 09:56:20 +0000 Inflammation is a complex biological response of tissue cells to harmful stimuli including trauma, tissue necrosis, and infections which plays a key role in the pathophysiology of many deadly diseases. In ethnomedicine Drynaria quercifolia fronds are used to treat inflammation as poultice on swellings and as antibacterial, hepatoprotective, and antipyretic agent. Herein, we have evaluated the antioedematous, antiproliferative, and analgesic properties of the ethanolic extract of fertile fronds of D. quercifolia (FF) by standard procedures. Oral administration of FF produced significant inhibition of carrageenan and histamine induced paw oedema in Wistar rats. FF significantly reduced both wet weight and dry weight of granuloma tissue which shows the inhibitory effect on exudative and proliferative phases of inflammation. FF significantly attenuated acute and delayed phases of formalin induced pain, acetic acid-induced writhing, capsaicin-induced nociception, and hot plate test in mice. Phytochemical analysis revealed the presence of coumarins, flavonoids, glycosides, phenolics, saponins, steroids, tannins, and terpenoids. Total phenolic content was 186 mg/g equivalent of gallic acid. The HPLC estimation showed flavanone glycoside naringin (1.2%) and its aglycone naringenin (0.02%). The presence of potent anti-inflammatory and analgesic principles in FF and their synergistic action may be the reason for the proposed therapeutic effects. G. I. Anuja, P. G. Latha, V. J. Shine, S. R. Suja, P. Shikha, K. Satheesh Kumar, and S. Rajasekharan Copyright © 2014 G. I. Anuja et al. All rights reserved. Crotalus durissus collilineatus Venom Induces TNF-α and IL-10 Production in Human Peripheral Blood Mononuclear Cells Sun, 19 Jan 2014 12:39:16 +0000 Snake venom has been the subject of numerous studies in an attempt to find properties and biological effects that may be beneficial to man. In this study we evaluated in vitro the effects of Crotalus durissus terrificus (Cdt) and Crotalus durissus collilineatus (Cdc) venom in human peripheral blood mononuclear cells (PBMCs). At 24 h, a significant decrease of viable cells was observed in cells stimulated with the Cdc venom at 0.0005 mg/mL and 0.005 mg/mL compared to the negative control. At 48 h, a significant decrease of viable cells was observed only in cells stimulated with Cdc venom at 0.005 mg/mL. A significant increase of TNF-α and IL-10 was detected 48 hours after culture of PBMC with Cdc, but not with Cdt venom. The expression of CD69 and PD1 (programmed death-1), activation and regulatory cell markers, on CD8+ and CD8− T cells did not change in the presence of Cdt and Cdc venom. Our results suggest the presence of proinflammatory and anti-inflammatory components in the Cdc venom. Further analysis should be done to identify those Cdc venom components as it has been done for the Cdt venom by other authors, indicating that modulatory components are found in the venom of different species of Crotalus snakes. Camila Bastos Ribeiro, Jéssica Cristina dos Santos, Jacyelle Medeiros Silva, Pedro Henrique Silva de Godoi, Marta Regina Magalhães, Mônica Spadafora-Ferreira, Simone Gonçalves Fonseca, and Irmtraut Araci Hoffman Pfrimer Copyright © 2014 Camila Bastos Ribeiro et al. All rights reserved. Nutrition, Inflammation, and Acute Pancreatitis Sun, 29 Dec 2013 11:14:27 +0000 Acute pancreatitis is acute inflammatory disease of the pancreas. Nutrition has a number of anti-inflammatory effects that could affect outcomes of patients with pancreatitis. Further, it is the most promising nonspecific treatment modality in acute pancreatitis to date. This paper summarizes the best available evidence regarding the use of nutrition with a view of optimising clinical management of patients with acute pancreatitis. Max Petrov Copyright © 2013 Max Petrov. All rights reserved. Low Serum Levels of Myeloid Progenitor Inhibitory Factor-1 Predict Good Response to Methotrexate in Rheumatoid Arthritis Tue, 24 Dec 2013 17:37:28 +0000 Background. Although the benchmark in the treatment of rheumatoid arthritis remains methotrexate, only 70% of patients respond. Thus, there is a need for predictive biomarkers. This study planned to evaluate serum levels of myeloid progenitor inhibitory factor-1 (MPIF-1) and monocyte chemoattractant protein 2 (MCP-2)—as biomarkers. Methods. Patients with rheumatoid arthritis (RA) having high disease activity (DAS28-3v ≥ 5.1) were treated with oral methotrexate (MTX) for 12 weeks. Disease activity was measured by DAS28-3v (Modified Disease Activity Score 3 variables). Serum samples were stored at baseline and 12 weeks. Results. This study included 46 patients (F : M = 35 : 11) having mean (±SD) age of 42.6 ± 11.3 yrs, disease duration of 4.7 ± 4.5 yrs, and DAS28-3v of 6.1 ± 0.8. Serum MPIF1 was elevated in patients compared to controls (1636.7 ± 1009.7, 441.2 ± 173.8 pg/mL, ), but there was no difference in MCP2 levels (31.4 ± 11.9, 33.8 ± 24.0 pg/mL). Baseline MPIF-1 level was lower in good responders (ΔDAS28-3v ≥ 1.2, ) compared to poor responders (ΔDAS28-3v < 0.6, ) (1171.0 ± 670.8, 1816.7 ± 1154.1 pg/mL, ). On ROC analysis, baseline MPIF1 performed reasonably to predict good response; that is, ΔDAS28-3v ≥ 1.2 (AUC 0.68, 95% CI 0.50–0.87). Conclusions. Lower baseline MPIF1 level predicted a good response to methotrexate at 12 weeks. Varun Dhir, Amit Sandhu, Nidhi Gupta, Veena Dhawan, Shefali Sharma, and Aman Sharma Copyright © 2013 Varun Dhir et al. All rights reserved. Adipose Tissue in Obesity-Related Inflammation and Insulin Resistance: Cells, Cytokines, and Chemokines Sun, 22 Dec 2013 09:20:06 +0000 Adipose tissue is a complex organ that comprises a wide range of cell types with diverse energy storage, metabolic regulation, and neuroendocrine and immune functions. Because it contains various immune cells, either adaptive (B and T lymphocytes; such as regulatory T cells) or innate (mostly macrophages and, more recently identified, myeloid-derived suppressor cells), the adipose tissue is now considered as a bona fide immune organ, at the cross-road between metabolism and immunity. Adipose tissue disorders, such as those encountered in obesity and lipodystrophy, cause alterations to adipose tissue distribution and function with broad effects on cytokine, chemokine, and hormone expression, on lipid storage, and on the composition of adipose-resident immune cell populations. The resulting changes appear to induce profound consequences for basal systemic inflammation and insulin sensitivity. The purpose of this review is to synthesize the current literature on adipose cell composition remodeling in obesity, which shows how adipose-resident immune cells regulate inflammation and insulin resistance—notably through cytokine and chemokine secretion—and highlights major research questions in the field. Kassem Makki, Philippe Froguel, and Isabelle Wolowczuk Copyright © 2013 Kassem Makki et al. All rights reserved. The Enigmatic Cytokine Oncostatin M and Roles in Disease Sun, 08 Dec 2013 10:53:16 +0000 Oncostatin M is a secreted cytokine involved in homeostasis and in diseases involving chronic inflammation. It is a member of the gp130 family of cytokines that have pleiotropic functions in differentiation, cell proliferation, and hematopoetic, immunologic, and inflammatory networks. However, Oncostatin M also has activities novel to mediators of this cytokine family and others and may have fundamental roles in mechanisms of inflammation in pathology. Studies have explored Oncostatin M functions in cancer, bone metabolism, liver regeneration, and conditions with chronic inflammation including rheumatoid arthritis, lung and skin inflammatory disease, atherosclerosis, and cardiovascular disease. This paper will review Oncostatin M biology in a historical fashion and focus on its unique activities, in vitro and in vivo, that differentiate it from other cytokines and inspire further study or consideration in therapeutic approaches. Carl D. Richards Copyright © 2013 Carl D. Richards. All rights reserved. A Review of the Inflammatory Chorioretinopathies: The White Dot Syndromes Thu, 31 Oct 2013 10:00:14 +0000 The white dot syndromes are a group of inflammatory chorioretinopathies of unknown etiology which have in common a unique and characteristic appearance of multiple yellow-white lesions affecting multiple layers of the retina, retinal pigment epithelium (RPE), choriocapillaris, and the choroid. They also have overlapping clinical features. We discuss acute retinal pigment epitheliopathy, multiple evanescent white dot syndrome, acute posterior multifocal placoid pigment epitheliopathy, multifocal choroiditis and panuveitis, acute zonal occult outer retinopathy, birdshot chorioretinopathy, and serpiginous choroidopathy. Some of these diseases are associated with a viral prodrome suggesting a possible viral/infectious etiology, while others are associated with a number of systemic processes suggesting an autoimmune etiology. We also review the presentation, evaluation/diagnosis, and treatment of these entities as well as the prognosis. Where applicable we discuss recent advancements in diagnosing and treating the white dot syndromes. Courtney M. Crawford and Okezie Igboeli Copyright © 2013 Courtney M. Crawford and Okezie Igboeli. All rights reserved. Curcumin Attenuation of Lipopolysaccharide Induced Cardiac Hypertrophy in Rodents Mon, 21 Oct 2013 09:55:40 +0000 To study the ameliorating effects of curcumin in lipopolysaccharide (LPS) induced cardiac hypertrophy, mice were assigned to 4 groups (3 males and 3 females in each group): (A) control, (B) curcumin: 100 μg/kg of body weight by intraperitoneal route (IP), (C) LPS: 60 mg/kg (IP), and (D) LPS + curcumin: both at previously stated concentrations by IP route. All mice were sacrificed as 12 hr and 24 hrs groups accordingly after LPS injection. The hearts were collected, photographed for cardiomegaly, and weighed to compare heart weight/brain weight (HW/BW) in mg/mg. For immunohistochemistry, the tissue sections were exposed to histone H3, H4 and acetylated histone H3, H4 antibody. LPS induced a significant increase in histone acetylation as shown by intense staining. In curcumin + LPS treated mice nuclear staining was similar to the control group indicating that curcumin traversed the histone acetylation activity of the LPS. To further check the mechanism of action of curcumin, p300 protein acetylation levels were analyzed. This study suggests that the probable mechanism of action of curcumin is via the reduction of p300 HAT activity. Rupak Chowdhury, Ramadevi Nimmanapalli, Thomas Graham, and Gopal Reddy Copyright © 2013 Rupak Chowdhury et al. All rights reserved. Evaluation of Artemisia amygdalina D. for Anti-Inflammatory and Immunomodulatory Potential Thu, 10 Oct 2013 15:05:38 +0000 Artemisia amygdalina D. is a critically endangered endemic medicinal plant of Kashmir Himalayas. In the current study anti-inflammatory and immunomodulatory activity of the plant was carried out. Carrageenan paw edema model was used to study the potential of the drug in inflammation in Wistar rats. SRBC-specific haemagglutination titre and DTH assays were carried out in Balb/C mice for observing the effect of test drugs on immune system. The plant extracts used as test drugs showed to have anti-inflammatory potential. The methanolic fraction was observed to have the maximum effect on the inhibition of paw edema formation with the inhibitory potential of 42.26%, while in the immunomodulation studies the test drugs were found to have the immunosuppressant activity with methanolic fraction again showing the maximum potential for the suppression of both humoral (55.89% and 47.91%) and cell-mediated immunity (62.27% and 57.21%). The plant in total seems to have the anti-inflammatory potential. The suppression of immune system suggests some mechanistic way by which the inhibition of inflammation takes place. Since, in chronic inflammation like arthritis, there is the involvement of immune system, the plant in that way may serve as an alternative for the treatment of such autoimmune diseases. Khan Mubashir, Bashir A. Ganai, Khalid Ghazanfar, Seema Akbar, Akhtar H. Malik, and Akbar Masood Copyright © 2013 Khan Mubashir et al. All rights reserved. Pentraxins: Structure, Function, and Role in Inflammation Sat, 14 Sep 2013 11:02:56 +0000 The pentraxins are an ancient family of proteins with a unique architecture found as far back in evolution as the Horseshoe crab. In humans the two members of this family are C-reactive protein and serum amyloid P. Pentraxins are defined by their sequence homology, their pentameric structure and their calcium-dependent binding to their ligands. Pentraxins function as soluble pattern recognition molecules and one of the earliest and most important roles for these proteins is host defense primarily against pathogenic bacteria. They function as opsonins for pathogens through activation of the complement pathway and through binding to Fc gamma receptors. Pentraxins also recognize membrane phospholipids and nuclear components exposed on or released by damaged cells. CRP has a specific interaction with small nuclear ribonucleoproteins whereas SAP is a major recognition molecule for DNA, two nuclear autoantigens. Studies in autoimmune and inflammatory disease models suggest that pentraxins interact with macrophage Fc receptors to regulate the inflammatory response. Because CRP is a strong acute phase reactant it is widely used as a marker of inflammation and infection. Terry W. Du Clos Copyright © 2013 Terry W. Du Clos. All rights reserved. Adipocytokines in Thyroid Dysfunction Sun, 23 Jun 2013 10:26:47 +0000 Adipocytokines are important mediators of interorgan crosstalk in metabolic regulation. Thyroid diseases have effects on metabolism and inflammation. The mechanism of these effects is not clear. Recently, there are several reports suggesting this interrelation between adipocytokines and thyroid dysfunction. In this review, we summarize this relation according to the literature. Berna İmge Aydogan and Mustafa Sahin Copyright © 2013 Berna İmge Aydogan and Mustafa Sahin. All rights reserved. Atherosclerosis, Dyslipidemia, and Inflammation: The Significant Role of Polyunsaturated Fatty Acids Sun, 12 May 2013 11:59:58 +0000 Phospholipids play an essential role in cell membrane structure and function. The length and number of double bonds of fatty acids in membrane phospholipids are main determinants of fluidity, transport systems, activity of membrane-bound enzymes, and susceptibility to lipid peroxidation. The fatty acid profile of serum lipids, especially the phospholipids, reflects the fatty acid composition of cell membranes. Moreover, long-chain n-3 polyunsatured fatty acids decrease very-low-density lipoprotein assembly and secretion reducing triacylglycerol production. N-6 and n-3 polyunsatured fatty acids are the precursors of signalling molecules, termed “eicosanoids,” which play an important role in the regulation of inflammation. Eicosanoids derived from n-6 polyunsatured fatty acids have proinflammatory actions, while eicosanoids derived from n-3 polyunsatured fatty acids have anti-inflammatory ones. Previous studies showed that inflammation contributes to both the onset and progression of atherosclerosis: actually, atherosclerosis is predominantly a chronic low-grade inflammatory disease of the vessel wall. Several studies suggested the relationship between long-chain n-3 polyunsaturated fatty acids and inflammation, showing that fatty acids may decrease endothelial activation and affect eicosanoid metabolism. Mariarita Dessì, Annalisa Noce, Pierfrancesco Bertucci, Simone Manca di Villahermosa, Rossella Zenobi, Veronica Castagnola, Eliana Addessi, and Nicola Di Daniele Copyright © 2013 Mariarita Dessì et al. All rights reserved. Paprika Pigments Attenuate Obesity-Induced Inflammation in 3T3-L1 Adipocytes Thu, 11 Apr 2013 10:43:03 +0000 Obesity is related to various diseases, such as diabetes, hyperlipidemia, and hypertension. Adipocytokine, which is released from adipocyte cells, affects insulin resistance and blood lipid level disorders. Further, adipocytokine is related to chronic inflammation in obesity condition adipocyte cells. Paprika pigments (PPs) contain large amounts of capsanthin and capsorubin. These carotenoids affect the liver and improve lipid disorders of the blood. However, how these carotenoids affect adipocyte cells remains unknown. Present study examined the effects of PP on adipocytokine secretion, which is related to improvement of metabolic syndrome. In addition, suppressive effects of PP on chronic inflammation in adipocyte cells were analyzed using 3T3-L1 adipocyte cells and macrophage cell coculture experiments. PP promoted 3T3-L1 adipocyte cells differentiation upregulated adiponectin mRNA expression and secretion. Further, coculture of adipocyte and macrophage cells treated with PP showed suppressed interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), monocyte chemotactic protein-1 (MCP-1), and resistin mRNA expression, similarly to treatment with troglitazone, which is a PPARγ ligand medicine. Conclusion. These results suggest that PP ameliorates chronic inflammation in adipocytes caused by obesity. PP adjusts adipocytokine secretion and might, therefore, affect antimetabolic syndrome diseases. Hayato Maeda, Shuuichi Saito, Nozomi Nakamura, and Takashi Maoka Copyright © 2013 Hayato Maeda et al. All rights reserved. Perioperative Dynamics of TLR2, TLR4, and TREM-1 Expression in Monocyte Subpopulations in the Setting of On-Pump Coronary Artery Bypass Surgery Sun, 17 Mar 2013 13:22:28 +0000 Hypercytokinemia plays a key role in the pathogenesis of systemic inflammatory response syndrome (SIRS). Monocytes are the main source of cytokines in the early inflammatory phase. Simultaneous stimulation of toll-like receptors (TLRs) and triggering receptor expressed on myeloid cells (TREM-1) activating receptor on monocytes results in the amplification of the inflammatory signal and multiple increase in proinflammatory cytokine production. The dynamics of those receptors expression on monocyte surface of patients with uncomplicated SIRS course followed coronary artery bypass surgery (CABG) was studied. The increase in TLR2 and TREM-1 expression on the first day after CABG induces proinflammatory and amplification potentials of monocytes in that period. The decrease in TLR2 surface expression on the seventh day compared to the preoperative values can be regarded as a mechanism limiting inflammatory response. The highest level of TLR2, TLR4, and TREM-1 surface expression was observed in CD14hiCD16+ monocyte subpopulation, confirming its proinflammatory profile. A. S. Golovkin, V. G. Matveeva, I. V. Kudryavtsev, M. N. Chernova, Y. V. Bayrakova, D. L. Shukevich, and E. V. Grigoriev Copyright © 2013 A. S. Golovkin et al. All rights reserved. High-Fat Fish Oil Diet Prevents Hypothalamic Inflammatory Profile in Rats Thu, 28 Feb 2013 08:45:45 +0000 Whether PUFA diets affect inflammatory mediators in central and peripheral sites is not clear. We investigated the effect of high-fat PUFA diets on the expression of proteins involved in inflammatory pathways in hypothalamus, muscle, and liver. Male rats were fed for 2 months with either chow or high-fat diets enriched with either soy (n-6 PUFAs) or fish oil (n-3 PUFAs). The fish group had normal body weight, low serum NEFA, reduced hypothalamic levels of TNF-α, IL-6, and TRAF6, and increased levels of IL-10 receptor. In contrast, the soy group had increased body weight and hypothalamic levels of TRAF6 and NFκBp65. In muscle, the fish diet reduced TNF-α and IL-6 levels. Both PUFA diets increased muscle IL-10 levels and reduced liver TNF-α and IL-6 levels. The data showed that the high-fat soy diet induced activation of the hypothalamic NFκB inflammatory pathway, a feature predisposing to feeding and energy expenditure disturbances associated with the development of obesity. On the other hand, the high-fat fish diet improved the central and the peripheral inflammatory profile via reduction of intracellular inflammatory mediators, suggesting a protection against obesity. Gustavo Duarte Pimentel, Fábio Santos Lira, José César Rosa, Cláudia Maria Oller do Nascimento, Lila Missae Oyama, Regina Lúcia Harumi Watanabe, and Eliane Beraldi Ribeiro Copyright © 2013 Gustavo Duarte Pimentel et al. All rights reserved. Monocyte Migration Driven by Galectin-3 Occurs through Distinct Mechanisms Involving Selective Interactions with the Extracellular Matrix Mon, 25 Feb 2013 09:54:38 +0000 Monocyte migration into tissues, an important event in inflammation, requires an intricate interplay between determinants on cell surfaces and extracellular matrix (ECM). Galectin-3 is able to modulate cell-ECM interactions and is an important mediator of inflammation. In this study, we sought to investigate whether interactions established between galectin-3 and ECM glycoproteins are involved in monocyte migration, given that the mechanisms by which monocytes move across the endothelium and through the extravascular tissue are poorly understood. Using the in vitro transwell system, we demonstrated that monocyte migration was potentiated in the presence of galectin-3 plus laminin or fibronectin, but not vitronectin, and was dependent on the carbohydrate recognition domain of the lectin. Only galectin-3-fibronectin combinations potentiated the migration of monocyte-derived macrophages. In binding assays, galectin-3 did not bind to fibronectin, whereas both the full-length and the truncated forms of the lectin, which retains carbohydrate binding ability, were able to bind to laminin. Our results show that monocytes migrate through distinct mechanisms and selective interactions with the extracellular matrix driven by galectin-3. We suggest that the lectin may bridge monocytes to laminin and may also activate these cells, resulting in the positive regulation of other adhesion molecules and cell adhesion to fibronectin. Cláudia Danella Polli, Karina Alves Toledo, Luís Henrique Franco, Vânia Sammartino Mariano, Leandro Licursi de Oliveira, Emerson Soares Bernardes, Maria Cristina Roque-Barreira, and Gabriela Pereira-da-Silva Copyright © 2013 Cláudia Danella Polli et al. All rights reserved. Nitric Oxide-Dependent Regulation of Cytokines Release in Type-II Diabetes Mellitus Sun, 17 Feb 2013 13:33:56 +0000 The mechanism of release of proinflammatory cytokines by blood granulocytes in diabetes is unknown. We investigated whether diabetes mellitus affects the production of cytokines by granulocytes (PMN) and mononuclear cells (PBMCs) and whether this is modulated by NO. Isolated PMN and PBMC from with or without type-II diabetes mellitus were incubated at 37°C for 6 h with S-nitroso-N-acetylpenicillamine (SNAP) at 0, 1, and 100 μM with or without lipopolysaccharides (LPS) stimulation (1 μg/mL). Supernatants were assayed for tumor necrosis factor-α (TNF-α) and interleukin-8 (IL-8) by sandwich ELISA. Significant increases in TNF-α and IL-8 were observed only in PMN from diabetic subjects with or without LPS stimulation and that exogenous NO inhibited further production of cytokines in a concentration-dependent manner. However, activity of PBMC when stimulated with LPS was greatly enhanced by diabetes, but not affected by NO production. Hence, suggesting that granulocytes activation and participation in diabetes related complications is modulated by NO bioavailability. Maqsood M. Elahi and Bashir M. Matata Copyright © 2013 Maqsood M. Elahi and Bashir M. Matata. All rights reserved. Effect of L. usitatissimum (Flaxseed/Linseed) Fixed Oil against Distinct Phases of Inflammation Sun, 17 Feb 2013 10:58:17 +0000 The present investigation summarizes the effect of Linum usitatissimum fixed oil against different phases of acute inflammatory reaction, namely, protein exudation, peritoneal capillary permeability, and leukocyte migration. The fixed oil exhibited dose-dependent inhibition of protein exudation vascular permeability, comparable to standard aspirin. The oil also inhibited the leukocyte migration in pleural exudates in a dose-dependent manner. Production of less vasodilatory (PGE3) and chemotactic (LTB5) eicosanoids through EPA (derived from linolenic acid) metabolism could account for the above observations. Gaurav Kaithwas and Dipak K. Majumdar Copyright © 2013 Gaurav Kaithwas and Dipak K. Majumdar. All rights reserved. Delayed Asthmatic Response to Allergen Challenge and Cytokines Released by Nonspecifically Stimulated Blood Cells Wed, 13 Feb 2013 08:39:37 +0000 Background. Bronchial asthma patients can develop various asthmatic response types following bronchial allergen challenge, such as immediate (IAR), late (LAR), dual late (DLAR), or delayed (DYAR), due to different immunologic mechanisms. The DYAR, recorded in 24 patients, beginning between 26 and 32 hrs and lasting up to 56 hrs after the bronchial allergen challenge, differs from the IAR, LAR, and DLAR in clinical, diagnostic, and immunologic aspects. Objective. To investigate amounts of particular cytokines released by the blood cells after an additional nonspecific stimulation with Phorbol 12-myristate 13-acetate (PMA) during the DYAR. Methods. In 24 patients, the repeated DYAR was supplemented with determination of cytokines both in the nonstimulated plasma and in the supernatants of the blood cells stimulated with PMA before and up to 72 hours after the bronchial challenge, by means of enzyme-linked immunoassay. Results. No significant changes of the prechallenge cytokine concentrations in the non-stimulated serum were recorded in the DYAR patients as compared with the healthy subjects. The DYAR was accompanied by significantly increased postchallenge concentrations () of IL-2, IL-8, IL-12p70, IL-13, IL-18, IFN-γ, G-CSF, TNF-α, and TGF-β, while decreased concentration of IL-7 () in the nonstimulated plasma. The significantly increased postchallenge concentrations of IL-2, IL-8, IL-12p70, IL-13, IL-18, IFN-γ, TNF-α, and TGF-β were released by peripheral blood cells after stimulation with PMA, as compared with both their prechallenge concentrations and with the PBS control values. Conclusions. These results would support evidence for an important role of the Th1 cells, neutrophils, monocytes, and probably also NK cells in the immunologic mechanism(s) leading to the development of the clinical DYAR. Nevertheless, an additional role of macrophages, endothelial and epithelial cells in these mechanisms cannot be even excluded. Zdenek Pelikan Copyright © 2013 Zdenek Pelikan. All rights reserved. A TREM-1 Polymorphism A/T within the Exon 2 Is Associated with Pneumonia in Burn-Injured Patients Tue, 12 Feb 2013 14:25:55 +0000 Background. The triggering receptor expressed in myeloid cells (TREM-1) is a key mediator in the activation of the local inflammatory response during lung infections. We aimed to evaluate the effect of a functionally relevant TREM-1 single nucleotide polymorphism within the exon 2 (A→T) on the development of pneumonia in burn patients. Objective. To determine whether a single nucleotide polymorphism (SNP) within the exon 2 (A→T) in the TREM-1 gene is associated with ventilator-associated pneumonia (VAP) in burn-injured patients. Methods. 540 patients with ≥10% total body surface area (TBSA) burn injuries or inhalation injury were prospectively enrolled. The influence of a polymorphism (A→T) in exon 2 of the TREM-1 gene was evaluated for association with increased risk of pneumonia by logistic regression analysis. Measurements and Main Results. 209 patients met criteria for VAP. Multivariate regression analysis showed that, after adjustment for potential confounders, we found that carriage of the TREM-1 T allele is associated with more than a 3-fold increased risk of VAP (OR 6.3, 95% CI 4–9). Conclusions. A TREM-1 single nucleotide polymorphism within the exon 2 (A→T) is associated with the development of pneumonia in burn patients. Fernando A. Rivera-Chávez, Ryan M. Huebinger, Agnes Burris, Ming-Mei Liu, Joseph P. Minei, John L. Hunt, Brett D. Arnoldo, and Robert C. Barber Copyright © 2013 Fernando A. Rivera-Chávez et al. All rights reserved. Marked Effects of Tachykinin in Myositis Both in the Experimental Side and Contralaterally: Studies on NK-1 Receptor Expressions in an Animal Model Tue, 29 Jan 2013 12:56:57 +0000 Muscle injury and inflammation (myositis) in a rabbit model of an unilateral muscle overuse were examined. It is unknown if the tachykinin system has a functional role in this situation. In this study, therefore, the neurokinin-1 receptor (NK-1R) expression patterns were evaluated. White blood cells, nerve fascicles, fine nerve fibers, and blood vessel walls in myositis areas showed NK-1R immunoreaction. NK-1R mRNA reactions were observable for white blood cells and blood vessel walls of these areas. NK-1R immunoreaction and NK-1R mRNA reactions were also seen for muscle fibers showing degenerative and regenerative features. There were almost no NK-1R immunoreactions in normal muscle tissue. Interestingly, marked NK-1R expressions were seen for myositis areas of both the experimental side and the contralateral nonexperimental side. EIA analyses showed that the concentration of substance P in the muscle tissue was clearly increased bilaterally at the experimental end stage, as compared to the situation for normal muscle tissue. These observations show that the tachykinin system is very much involved in the processes that occur in muscle injury/myositis. The effects can be related to proinflammatory effects and/or tissue repair. The fact that there are also marked NK-1R expressions contralaterally indicate that the tachykinin system has crossover effects. Yafeng Song, Per S. Stål, Jiguo Yu, and Sture Forsgren Copyright © 2013 Yafeng Song et al. All rights reserved. Interleukin-17 Expression in the Barrett’s Metaplasia-Dysplasia-Adenocarcinoma Sequence Thu, 27 Dec 2012 16:06:01 +0000 Introduction. This pilot study evaluated the expression of the proinflammatory cytokine IL-17 along the Barrett’s metaplasia-dysplasia-adenocarcinoma sequence by establishing the expression levels of IL-17 in columnar epithelium, intestinal metaplastic cells, and dysplastic/glandular neoplastic cells. Immunohistochemical techniques were used to examine the accumulation of the proinflammatory cytokine IL-17 in forty () formalin-fixed, paraffin-embedded oesophageal archived specimens across a range of endoscopic diagnostic categories, and a highly significant difference was found, where , in IL-17 expression (Kruskall Wallis and Mann-Whitney ) between all the cell types examined. There was also a strong positive correlation (Spearman's rank correlation) between disease progression and IL-17 expression (, , ), IL-17 expression was absent or absent/weak in columnar epithelium, weak to moderate in columnar metaplastic cells, and moderate to strong in dysplastic/neoplastic cells, which demonstrated that the elevation of IL-17 expression occurs in the progression of the disease. Understanding the differential expression of IL-17 between benign and malignant tissue potentially has a significant diagnostic, prognostic, and therapeutic value. Ultimately, this selective biomarker may be employed in routine clinical practice for the screening of oesophageal adenocarcinoma. J. R. Bannister, A. L. Khan, D. W. Eccleston, R. K. Deol-Poonia, and S. F. Hughes Copyright © 2012 J. R. Bannister et al. All rights reserved. sTREM-1 as a Prognostic Marker of Postoperative Complications in Cardiac Surgery Mon, 17 Dec 2012 14:01:00 +0000 Cell-activating receptor TREM-1 (triggering receptor expressed on myeloid cells 1) regulates congenital immune response and contributes to systemic inflammatory response syndrome (SIRS) development. It is able to multiply cytokine production while stimulated together with the main receptors of the congenital immune system. The purpose of the paper is to study the potential use of soluble TREM-1 (sTREM-1) as a marker of intensive SIRS and a criterion for postoperative complications prediction following on-pump coronary artery bypass surgery (CABG). Results show that early postoperative sTREM-1 concentrations demonstrate their potential prognostic value regarding SIRS-associated complications. A. S. Golovkin, V. G. Matveeva, E. V. Grigoriev, D. L. Shukevich, Y. V. Bayrakova, and L. S. Barbarash Copyright © 2012 A. S. Golovkin et al. All rights reserved. Angiotensin Type 1a Receptor Signaling Is Not Necessary for the Production of Reactive Oxygen Species in Polymorphonuclear Leukocytes Tue, 04 Dec 2012 11:30:32 +0000 Background. Although angiotensin II (Ang II) has inflammatory effects, little is known about its role in polymorphonuclear leucocytes (PMLs). To elucidate the role of Ang II in PMLs ROS production, we examined hydrogen peroxide (H2O2), one of the ROS, and NO production in AT1a receptor knockout (AT1KO) mice. Methods and Results. PMLs were analyzed from Ang II type 1a receptor knockout mice (AT1KO) and C57BL/6 wild type mice. Using flow cytometry, we studied hydrogen peroxide (H2O2) production from PMLs after Staphylococcus aureus phagocytosis or phorbol myristate acetate (PMA) stimulation. Nitric oxide (NO) production in the AT1KO was low at basal and after phagocytosis. In the AT1KO, basal H2O2 production was low. After PMA or phagocytosis stimulation, however, H2O2 production was comparable to wild type mice. Next we studied the H2O2 production in C57BL/6 mice exposed to Ang II or saline. H2O2 production stimulated by PMA or phagocytosis did not differ between the two groups. Conclusions. AT1a pathway is not necessary for PMLs H2O2 production but for NO production. There was a compensatory pathway for H2O2 production other than the AT1a receptor. Fumiko Yamato, Junji Takaya, Shoji Tsuji, Masafumi Hasui, and Kazunari Kaneko Copyright © 2012 Fumiko Yamato et al. All rights reserved. Lysophosphatidic Acid Stimulates MCP-1 Secretion from C2C12 Myoblast Sun, 25 Nov 2012 10:06:04 +0000 Chemokines are regulatory proteins that play an important role in muscle cell migration and proliferation. In this study, C2C12 cells treated with lysophosphatidic acid (LPA) showed an increase in endogenous monocyte chemotactic protein-1 (MCP-1) expression and secretion. LPA is a naturally occurring bioactive lysophospholipid with hormone- and growth-factor-like activities. LPA is produced by activated platelets, cytokine-stimulated leukocytes, and possibly by other cell types. However, the LPA analog cyclic phosphatidic acid (cPA) had no effect on the expression and secretion of MCP-1. LPA, although similar in structure to cPA, had potent inducing effects on MCP-1 expression in C2C12 cells. In this study, we showed that LPA enhanced MCP-1 mRNA expression and protein secretion in a dose-dependent manner. Taken together, these results suggest that LPA enhances MCP-1 secretion in C2C12 cells and thus may play an important role in cell proliferation. Tamotsu Tsukahara and Hisao Haniu Copyright © 2012 Tamotsu Tsukahara and Hisao Haniu. All rights reserved. Gadolinium Chloride Attenuates Sepsis-Induced Pulmonary Apoptosis and Acute Lung Injury Thu, 01 Nov 2012 15:00:29 +0000 Gadolinium chloride (GdCl3), a Kupffer cells inhibitor, attenuates acute lung injury; however, the mechanisms behind this effect are not completely elucidated. We tested the hypothesis that GdCl3 acts through the inhibition of lung parenchymal cellular apoptosis. Two groups of rats were injected intraperitoneally with saline or E. coli lipopolysaccharide. In two additional groups, rats were injected with GdCl3 24 hrs prior to saline or LPS administration. At 12 hrs, lung injury, inflammation, and apoptosis were studied. Lung water content, myeloperoxidase activity, pulmonary apoptosis and mRNA levels of interleukin-1β, -2, -5, -6, -10 and TNF-α rose significantly in LPS-injected animals. Pretreatment with GdCl3 significantly reduced LPS-induced elevation of pulmonary water content, myeloperoxidase activity, cleaved caspase-3 intensity, and attenuated pulmonary TUNEL-positive cells. GdCl3 pre-treatment upregulated IL-1β, -2 and -10 pulmonary gene expression without significantly affecting the others. These results suggest that GdCl3 attenuates acute lung injury through its effects on pulmonary parenchymal apoptosis. Osama A. Kishta, Peter Goldberg, and Sabah N. A. Husain Copyright © 2012 Osama A. Kishta et al. All rights reserved.