Mediators of Inflammation The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Trachoma and Ocular Chlamydial Infection in the Era of Genomics Thu, 03 Sep 2015 09:35:14 +0000 Trachoma is a blinding disease usually caused by infection with Chlamydia trachomatis (Ct) serovars A, B, and C in the upper tarsal conjunctiva. Individuals in endemic regions are repeatedly infected with Ct throughout childhood. A proportion of individuals experience prolonged or severe inflammatory episodes that are known to be significant risk factors for ocular scarring in later life. Continued scarring often leads to trichiasis and in-turning of the eyelashes, which causes pain and can eventually cause blindness. The mechanisms driving the chronic immunopathology in the conjunctiva, which largely progresses in the absence of detectable Ct infection in adults, are likely to be multifactorial. Socioeconomic status, education, and behavior have been identified as contributing to the risk of scarring and inflammation. We focus on the contribution of host and pathogen genetic variation, bacterial ecology of the conjunctiva, and host epigenetic imprinting including small RNA regulation by both host and pathogen in the development of ocular pathology. Each of these factors or processes contributes to pathogenic outcomes in other inflammatory diseases and we outline their potential role in trachoma. Tamsyn Derrick, Chrissy h. Roberts, Anna R. Last, Sarah E. Burr, and Martin J. Holland Copyright © 2015 Tamsyn Derrick et al. All rights reserved. IL-4 Inhibits IL-1β-Induced Depressive-Like Behavior and Central Neurotransmitter Alterations Mon, 31 Aug 2015 07:35:41 +0000 It has been known that activation of the central innate immune system or exposure to stress can disrupt balance of anti-/proinflammatory cytokines. The aim of the present study was to investigate the role of pro- and anti-inflammatory cytokines in the modulation of depressive-like behaviors, the hormonal and neurotransmitter systems in rats. We investigated whether centrally administered IL-1β is associated with activation of CNS inflammatory pathways and behavioral changes and whether treatment with IL-4 could modulate IL-1β-induced depressive-like behaviors and central neurotransmitter systems. Infusion of IL-4 significantly decreased IL-1β-induced anhedonic responses and increased social exploration and total activity. Treatment with IL-4 markedly blocked IL-1β-induced increase in PGE2 and CORT levels. Also, IL-4 reduced IL-1β-induced 5-HT levels by inhibiting tryptophan hydroxylase (TPH) mRNA and activating serotonin transporter (SERT) in the hippocampus, and levels of NE were increased by activating tyrosine hydroxylase (TH) mRNA expression. These results demonstrate that IL-4 may locally contribute to the regulation of noradrenergic and serotonergic neurotransmission and may inhibit IL-1β-induced behavioral and immunological changes. The present results suggest that IL-4 modulates IL-1β-induced depressive behavior by inhibiting IL-1β-induced central glial activation and neurotransmitter alterations. IL-4 reduced central and systemic mediatory inflammatory activation, as well as reversing the IL-1β-induced alterations in neurotransmitter levels. The present findings contribute a biochemical pathway regulated by IL-4 that may have therapeutic utility for treatment of IL-1β-induced depressive behavior and neuroinflammation which warrants further study. Hyun-Jung Park, Hyun-Soo Shim, Kyungeh An, Angela Starkweather, Kyung Soo Kim, and Insop Shim Copyright © 2015 Hyun-Jung Park et al. All rights reserved. PGE2 Elevates IL-23 Production in Human Dendritic Cells via a cAMP Dependent Pathway Thu, 27 Aug 2015 12:28:17 +0000 PGE2 elevates IL-23 production in mouse dendritic cells while inhibits IL-23 production in isolated human monocytes. Whether this differential effect of PGE2 on IL-23 production is cell-type- or species-specific has not been investigated in detail. The present study was designed to investigate the effect of PGE2 on IL-23 production in human DCs and the possible underlying mechanisms. Human monocytes derived dendritic cells (Mo-DCs) were pretreated with or without PGE2. Then the cells were incubated with zymosan. Our results demonstrated that PGE2 promoted zymosan-induced IL-23 production in a concentration dependent manner. In addition, it was found that PGE2 is also able to elevate MyD88-mediated IL-23 p19 promoter activity. More importantly, ELISA data demonstrated that db-cAMP, a cAMP analog, and forskolin, an adenylate cyclase activator, can mimic the effect of PGE2 on zymosan-induced IL-23 production, and rp-cAMP, a protein kinase A (PKA) inhibitor, can block the effect of PGE2. Moreover, PGE2 can increase zymosan-induced expression of the mRNA levels of both p19 and p40 subunits, which was mimicked by db-cAMP and forskolin. Our data suggest that PGE2 elevates the production of IL-23 in human Mo-DCs via a cAMP dependent pathway. Quanxing Shi, Zhao Yin, Bei Zhao, Fei Sun, Haisheng Yu, Xiangyun Yin, Liguo Zhang, and Shouli Wang Copyright © 2015 Quanxing Shi et al. All rights reserved. Transcriptional Regulatory Network for the Development of Innate Lymphoid Cells Wed, 26 Aug 2015 07:09:31 +0000 Recent studies on innate lymphoid cells (ILCs) have expanded our knowledge about the innate arm of the immune system. Helper-like ILCs share both the “innate” feature of conventional natural killer (cNK) cells and the “helper” feature of CD4+ T helper (Th) cells. With this combination, helper-like ILCs are capable of initiating early immune responses similar to cNK cells, but via secretion of a set of effector cytokines similar to those produced by Th cells. Although many studies have revealed the functional similarity between helper-like ILCs and Th cells, some aspects of ILCs including the development of this lineage remain elusive. It is intriguing that the majority of transcription factors involved in multiple stages of T cell development, differentiation, and function also play critical roles during ILC development. Regulators such as Id2, GATA-3, Nfil3, TOX, and TCF-1 are expressed and function at various stages of ILC development. In this review, we will summarize the expression and functions of these transcription factors shared by ILCs and Th cells. We will also propose a complex transcriptional regulatory network for the lineage commitment of ILCs. Chao Zhong and Jinfang Zhu Copyright © 2015 Chao Zhong and Jinfang Zhu. All rights reserved. An Inflammatory Polymorphisms Risk Scoring System for the Differentiation of Ischemic Stroke Subtypes Wed, 19 Aug 2015 09:23:28 +0000 Inflammation has been associated with atherothrombotic stroke and recently with cardioembolic stroke. Different genetic risk factors have been specifically associated with the subtypes of ischemic stroke (cardioembolic, atherothrombotic, and lacunar). However, there are no studies that have generated genetic risk scores for the different subtypes of ischemic stroke using polymorphisms associated with inflammation. Methods. We have analyzed 68 polymorphisms of 30 inflammatory mediator genes in 2,685 subjects: 1,987 stroke cases and 698 controls. We generated a genetic scoring system with the most significant polymorphisms weighted by the odds ratio of every polymorphism and taken into consideration the stroke subtype. Results. Three polymorphisms, rs1205 (CRP gene), rs1800779, and rs2257073 (NOS3 gene), were associated with cardioembolic stroke ( value ). The score generated was only associated with the cardioembolic stroke subtype ( value: 0.001) and was replicated in an independent cohort ( value: 0.017). The subjects with the highest score presented a cardioembolic stroke in 92.2% of the cases ( value: 0.002). Conclusion. The genetics of inflammatory markers is more closely associated with cardioembolic strokes than with atherothrombotic or lacunar strokes. The genetic risk scoring system could be useful in the prediction and differentiation of ischemic stroke; however, it might be specific to particular ischemic stroke subtypes. Elena Muiño, Jurek Krupinski, Caty Carrera, Cristina Gallego-Fabrega, Joan Montaner, and Israel Fernández-Cadenas Copyright © 2015 Elena Muiño et al. All rights reserved. Basic Characteristics of Adults with Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Adenopathy Syndrome in Comparison with the Typical Pediatric Expression of Disease Tue, 18 Aug 2015 08:37:48 +0000 Autoinflammatory diseases are caused by inflammasome dysregulation leading to overproduction of proinflammatory cytokines and a pathological delay in the inflammation switching off. The progress of cellular biology has partially clarified pathogenic mechanisms behind monogenic autoinflammatory diseases, whereas little is known about the polygenic ones. Although the genetic susceptibility of periodic fever, aphthous stomatitis, pharyngitis, and adenopathy (PFAPA) syndrome is still obscure, the presence of overlapping symptoms with monogenic periodic fevers, the recurrence in family members, the important role played by dysregulated interleukin- (IL-) 1β secretion during flares, the overexpression of inflammasome-associated genes during attacks, and, last but not least, the therapeutic efficacy of IL-1β blockade strongly indicate a potential genetic involvement in its pathogenesis, probably linked with environmental factors. PFAPA syndrome has a typical inception in the pediatric age, but a delayed onset during adulthood has been described as well. Treatments required as well as effectiveness of tonsillectomy remain controversial, even if the disease seems to have a self-limited course mostly in children. The purpose of this review is to provide an overview of this complex polygenic/multifactorial autoinflammatory disorder in which the innate immune system undoubtedly plays a basic role. Marco Cattalini, Martina Soliani, Donato Rigante, Giuseppe Lopalco, Florenzo Iannone, Mauro Galeazzi, and Luca Cantarini Copyright © 2015 Marco Cattalini et al. All rights reserved. IL-17A, IL-22, IL-6, and IL-21 Serum Levels in Plaque-Type Psoriasis in Brazilian Patients Thu, 13 Aug 2015 13:30:02 +0000 Psoriasis is a chronic inflammatory skin disease characterized by alterations in cytokines produced by both Th1 and Th17 pathways. The aim of this study was to evaluate serum levels of pivotal cytokines and correlate them with clinical parameters. Serum samples from 53 psoriasis patients and 35 healthy volunteers, matched by the proportion of sex and age ratios, were collected for ELISA cytokine detection. Psoriasis Area and Severity Index (PASI) was assessed at the time of sampling in psoriasis patients. Our findings demonstrate that IL-17A, IL-22, and IL-6 serum concentrations were significantly higher in psoriasis patients than in the control group. No statistical correlation could be found between cytokines concentrations, PASI score, and age in this study. Although our results do not show any correlation between serum levels of IL-17A, IL-22, and IL-6 and disease activity, the present study confirms that they were increased in Brazilian psoriasis patients in comparison to healthy volunteers. Priscilla Stela Santana de Oliveira, Pablo Ramon Gualberto Cardoso, Emerson Vasconcelos de Andrade Lima, Michelly Cristiny Pereira, Angela Luzia Branco Pinto Duarte, Ivan da Rocha Pitta, Moacyr Jesus Barreto de Melo Rêgo, and Maira Galdino da Rocha Pitta Copyright © 2015 Priscilla Stela Santana de Oliveira et al. All rights reserved. Synthesis and Validation of a Hydroxypyrone-Based, Potent, and Specific Matrix Metalloproteinase-12 Inhibitor with Anti-Inflammatory Activity In Vitro and In Vivo Thu, 13 Aug 2015 10:06:04 +0000 A hydroxypyrone-based matrix metalloproteinase (MMP) inhibitor was synthesized and assayed for its inhibitory capacity towards a panel of ten different MMPs. The compound exhibited selective inhibition towards MMP-12. The effects of inhibition of MMP-12 on endotoxemia and inflammation-induced blood-cerebrospinal fluid barrier (BCSFB) disruption were assessed both in vitro and in vivo. Similar to MMP-12 deficient mice, inhibitor-treated mice displayed significantly lower lipopolysaccharide- (LPS-) induced lethality compared to vehicle treated controls. Following LPS injection Mmp-12 mRNA expression was massively upregulated in choroid plexus tissue and a concomitant increase in BCSFB permeability was observed, which was restricted in inhibitor-treated mice. Moreover, an LPS-induced decrease in tight junction permeability of primary choroid plexus epithelial cells was attenuated by inhibitor application in vitro. Taken together, this hydroxypyrone-based inhibitor is selective towards MMP-12 and displays anti-inflammatory activity in vitro and in vivo. J. Aerts, R. E. Vandenbroucke, R. Dera, S. Balusu, E. Van Wonterghem, L. Moons, C. Libert, W. Dehaen, and L. Arckens Copyright © 2015 J. Aerts et al. All rights reserved. Monosodium Urate in the Presence of RANKL Promotes Osteoclast Formation through Activation of c-Jun N-Terminal Kinase Wed, 12 Aug 2015 07:19:27 +0000 The aim of this study was to clarify the role of monosodium urate (MSU) crystals in receptor activator of nuclear factor kB ligand- (RANKL-) RANK-induced osteoclast formation. RAW 264.7 murine macrophage cells were incubated with MSU crystals or RANKL and differentiated into osteoclast-like cells as confirmed by staining for tartrate-resistant acid phosphatase (TRAP) and actin ring, pit formation assay, and TRAP activity assay. MSU crystals in the presence of RANKL augmented osteoclast differentiation, with enhanced mRNA expression of NFATc1, cathepsin K, carbonic anhydrase II, and matrix metalloproteinase-9 (MMP-9), in comparison to RAW 264.7 macrophages incubated in the presence of RANKL alone. Treatment with both MSU crystals and RANKL induced osteoclast differentiation by activating downstream molecules in the RANKL-RANK pathway including tumor necrosis factor receptor-associated factor 6 (TRAF-6), JNK, c-Jun, and NFATc1. IL-1b produced in response to treatment with both MSU and RANKL is involved in osteoclast differentiation in part through the induction of TRAF-6 downstream of the IL-1b pathway. This study revealed that MSU crystals contribute to enhanced osteoclast formation through activation of RANKL-mediated pathways and recruitment of IL-1b. These findings suggest that MSU crystals might be a pathologic causative agent of bone destruction in gout. Jung-Yoon Choe, Ki-Yeun Park, and Seong-Kyu Kim Copyright © 2015 Jung-Yoon Choe et al. All rights reserved. Modulation of Cytokines Production by Indomethacin Acute Dose during the Evolution of Ehrlich Ascites Tumor in Mice Wed, 12 Aug 2015 06:27:54 +0000 The aim of the present study was to investigate the influence of a nonselective COX1/COX2 inhibitor (indomethacin) on tumor growth of Ehrlich Ascites Tumor (EAT) in mice, using as parameters the tumor growth and cytokine profile. Mice were inoculated with EAT cells and treated with indomethacin. After 1, 3, 6, 10, and 13 days the animals were evaluated for the secretion of TNFα, IL-1α, IL-2, IL-4, IL-6, IL-10, and IL-13 and PGE2 level in peritoneal cavity. The results have shown that EAT induces PGE2 production and increases tumor cells number from the 10th day. The cytokine profile showed EAT induces production of IL-6 from 10th day and of IL-2 on 13th day; the other studied cytokines were not affected in a significant way. The indomethacin treatment of EAT-bearing mice inhibited the tumor growth and PGE2 synthesis from the 10th day. In addition, the treatment of EAT-bearing mice with indomethacin has stimulated the IL-13 production and has significantly inhibited IL-6 in the 13th day of tumor growth. Taken together, the results have demonstrated that EAT growth is modulated by PGE2 and the inhibition of the tumor growth could be partly related to suppression of IL-6 and induction of IL-13. Luciana Boffoni Gentile, Nicolle Queiroz-Hazarbassanov, Cristina de Oliveira Massoco, and Denise Fecchio Copyright © 2015 Luciana Boffoni Gentile et al. All rights reserved. Mediators of Inflammation in Pulmonary Diseases Mon, 10 Aug 2015 12:17:03 +0000 Kostas Spiropoulos, Nikolaos Siafakas, Marc Miravitlles, Francesco Blasi, and Kiriakos Karkoulias Copyright © 2015 Kostas Spiropoulos et al. All rights reserved. A Subgroup of Latently Mycobacterium tuberculosis Infected Individuals Is Characterized by Consistently Elevated IgA Responses to Several Mycobacterial Antigens Mon, 10 Aug 2015 06:53:52 +0000 Elevated antibody responses to Mycobacterium tuberculosis antigens in individuals with latent infection (LTBI) have previously been linked to an increased risk for progression to active disease. Studies in the field focussed mainly on IgG antibodies. In the present study, IgA and/or IgG responses to the mycobacterial protein antigens AlaDH, NarL, 19 kDa, PstS3, and MPT83 were determined in a blinded fashion in sera from 53 LTBI controls, 14 healthy controls, and 42 active TB subjects. Among controls, we found that elevated IgA levels against all investigated antigens were not randomly distributed but concentrated on a subgroup of —with particular high levels in a small subgroup of comprising one progressor to active TB. Based on a specificity of , anti-NarL IgA antibodies achieved with sensitivity the highest accuracy for the detection of active TB compared to healthy controls. In conclusion, the consistently elevated IgA levels in a subgroup of controls suggest higher mycobacterial load, a risk factor for progression to active TB, and together with high IgG levels may have prognostic potential and should be investigated in future large scale studies. The novel antigen NarL may also be promising for the antibody-based diagnosis of active TB cases. Ralf Baumann, Susanne Kaempfer, Novel N. Chegou, Wulf Oehlmann, Ralf Spallek, André G. Loxton, Paul D. van Helden, Gillian F. Black, Mahavir Singh, and Gerhard Walzl Copyright © 2015 Ralf Baumann et al. All rights reserved. Chlamydia pneumoniae-Mediated Inflammation in Atherosclerosis: A Meta-Analysis Sun, 09 Aug 2015 06:03:14 +0000 Several studies have attempted to relate the C. pneumoniae-mediated inflammatory state with atherosclerotic cardiovascular diseases, providing inconsistent results. Therefore, we performed a meta-analysis to clarify whether C. pneumoniae may contribute to the pathogenesis of atherosclerosis by enhancing inflammation. 12 case-control, 6 cross-sectional, and 7 prospective studies with a total of 10,176 patients have been included in this meta-analysis. Odds Ratio (OR) with a 95% confidence interval was used to assess the seroprevalence of C. pneumoniae and differences between levels of inflammatory markers were assessed by standard mean differences. Publication bias was performed to ensure the statistical power. hsCRP, fibrinogen, interleukin- (IL-) 6, TNF-α, and IFN-γ showed a significant increase in patients with atherosclerosis compared to healthy controls (), along with a higher seroprevalence of C. pneumoniae (OR of 3.11, 95% CI: 2.88–3.36, ). More interestingly, hsCRP, IL-6, and fibrinogen levels were significantly higher in C. pneumoniae IgA seropositive compared to seronegative atherosclerotic patients (). In conclusion, the present meta-analysis suggests that C. pneumoniae infection may contribute to atherosclerotic cardiovascular diseases by enhancing the inflammatory state, and, in particular, seropositivity to C. pneumoniae IgA, together with hsCRP, fibrinogen, and IL-6, may be predictive of atherosclerotic cardiovascular risk. Simone Filardo, Marisa Di Pietro, Alessio Farcomeni, Giovanna Schiavoni, and Rosa Sessa Copyright © 2015 Simone Filardo et al. All rights reserved. Lack of Association between Polymorphisms of the TLR4 Gene and Infection with the Hepatitis B and C Viruses Thu, 06 Aug 2015 13:48:17 +0000 Toll-like receptor 4 (TLR4) plays a crucial role in the early recognition of pathogenic microorganisms and provides an ideal model to investigate the consequences of genetic variation and susceptibility to diseases. The present study investigated the occurrence of the single nucleotide polymorphisms (SNPs) rs4986790 (A>G) and rs4986791 (C>T) in the TLR4 gene in chronic carriers of the hepatitis B (HBV) and C (HCV) viruses. A total of 420 blood samples were collected (HBV, 49; HCV, 72; and controls, 299) at the liver disease outpatient clinic of Hospital da Fundação Santa Casa de Misericórdia do Pará (FSCMPA). Genomic DNA extracted from leukocytes was subjected to real-time polymerase chain reaction (qPCR) analysis to identify the genetic profile of the participants. No significant differences were found in the allele and genotype frequencies between the infected participants and controls. No significant associations were found between the investigated polymorphisms and inflammatory activity, fibrosis, and the presence of cirrhosis; the same results were obtained in the haplotype analysis. The results showed a lack of association between the rs4986790 and rs4986791 SNPs and susceptibility to infection with HBV and HCV, as well as clinical and laboratory information of the patients. Orlando de Souza Pires-Neto, Keyla Santos Guedes de Sá, Barbara Brasil Santana, Samara Tatielle Monteiro Gomes, Ednelza da Silva Graça Amoras, Simone Regina da Silva Conde, Sâmia Demachki, Vânia Nakauth Azevedo, Rosimar Neris Martins-Feitosa, Marluísa de Oliveira Guimarães Ishak, Ricardo Ishak, and Antonio Carlos Rosário Vallinoto Copyright © 2015 Orlando de Souza Pires-Neto et al. All rights reserved. Expression Pattern of Fatty Acid Binding Proteins in Celiac Disease Enteropathy Wed, 05 Aug 2015 14:15:12 +0000 Celiac disease (CD) is an immune-mediated enteropathy that develops in genetically susceptible individuals following exposure to dietary gluten. Severe changes at the intestinal mucosa observed in untreated CD patients are linked to changes in the level and in the pattern of expression of different genes. Fully differentiated epithelial cells express two isoforms of fatty acid binding proteins (FABPs): intestinal and liver, IFABP and LFABP, respectively. These proteins bind and transport long chain fatty acids and also have other important biological roles in signaling pathways, particularly those related to PPAR and inflammatory processes. Herein, we analyze the serum levels of IFABP and characterize the expression of both FABPs at protein and mRNA level in small intestinal mucosa in severe enteropathy and normal tissue. As a result, we observed higher levels of circulating IFABP in untreated CD patients compared with controls and patients on gluten-free diet. In duodenal mucosa a differential FABPs expression pattern was observed with a reduction in mRNA levels compared to controls explained by the epithelium loss in severe enteropathy. In conclusion, we report changes in FABPs’ expression pattern in severe enteropathy. Consequently, there might be alterations in lipid metabolism and the inflammatory process in the small intestinal mucosa. Natalia M. Bottasso Arias, Marina García, Constanza Bondar, Luciana Guzman, Agustina Redondo, Nestor Chopita, Betina Córsico, and Fernando G. Chirdo Copyright © 2015 Natalia M. Bottasso Arias et al. All rights reserved. Inflammatory Mediators in Autoimmunity and Systemic Autoimmune Diseases Wed, 05 Aug 2015 06:21:21 +0000 Britt Nakken, György Nagy, Peter C. Huszthy, Even Fossum, Yrjö Konttinen, and Peter Szodoray Copyright © 2015 Britt Nakken et al. All rights reserved. Periodontal Disease and Its Systemic Associated Diseases Tue, 04 Aug 2015 13:25:07 +0000 Javier Fernandez-Solari, Paula Barrionuevo, and Claudio A. Mastronardi Copyright © 2015 Javier Fernandez-Solari et al. All rights reserved. C-Reactive Protein in Peripheral Blood of Patients with Chronic and Aggressive Periodontitis, Gingivitis, and Gingival Recessions Tue, 04 Aug 2015 11:36:29 +0000 CRP is a plasma protein that reflects a measure of the acute phase response to inflammation and is one of the markers of choice in monitoring this response. CRP can be used for the prediction and early detection of periodontal disease. The aim of this study was to compare and evaluate the systemic levels of CRP in the peripheral blood samples of patients with chronic and aggressive periodontitis, gingivitis, and gingival recessions and compare them with periodontal clinical parameters. All patients () were examined prior to the initiation of periodontal treatment. Patients were divided into four groups. Group A consisted of 26 patients with aggressive periodontitis, Group B consisted of 111 patients with chronic periodontitis, Group C consisted of 13 patients with gingivitis, and Group D consisted of 8 patients with gingival recessions. Our study results indicate that CRP levels increase subsequently with the severity of the periodontal disease and that the bleeding on probing index showed much better positive correlation with the CRP levels compared to the pocket depth index in both periodontitis patients groups, especially in aggressive periodontitis patients. Stepan Podzimek, Jaroslav Mysak, Tatjana Janatova, and Jana Duskova Copyright © 2015 Stepan Podzimek et al. All rights reserved. Periodontal Diseases and Dental Caries in Children with Type 1 Diabetes Mellitus Tue, 04 Aug 2015 11:18:55 +0000 Type 1 diabetes mellitus is a chronic metabolic disease of an autoimmune origin with early manifestation predominantly in the childhood. Its incidence has been rising in most European countries. Diabetes has been intensively studied by all branches of medicine. There were a number of studies investigating oral consequences of diabetes; however, unambiguous conclusions were drawn only for the relationship between diabetes and periodontal impairment. Many studies confirmed higher plaque levels and higher incidence of chronic gingivitis both in adults and in children with diabetes. Juvenile periodontitis is rare both in healthy subjects and in those with type 1 diabetes. Yet certain findings from well-conducted studies, for example, differences in oral microflora or the impact of metabolic control of diabetes on periodontal health, indicate a higher risk of periodontitis in children with type 1 diabetes. As for the association of diabetes and dental caries, the results of the studies are inconsistent. However, it was found that some risk factors for dental caries are either more or less prevalent in the diabetic population. Despite an extensive research in this area we have to acknowledge that many questions have remained unanswered. There is a need for continued, thorough research in this area. Marta Novotna, Stepan Podzimek, Zdenek Broukal, Erika Lencova, and Jana Duskova Copyright © 2015 Marta Novotna et al. All rights reserved. Relationship between Periodontitis and Rheumatoid Arthritis: Review of the Literature Tue, 04 Aug 2015 10:36:27 +0000 Periodontitis (PD) and rheumatoid arthritis (RA) are immunoinflammatory diseases where leukocyte infiltration and inflammatory mediators induce alveolar bone loss, synovitis, and joint destruction, respectively. Thus, we reviewed the relationship between both diseases considering epidemiological aspects, mechanical periodontal treatment, inflammatory mediators, oral microbiota, and antibodies, using the keywords “periodontitis” and “rheumatoid arthritis” in PubMed database between January 2012 and March 2015, resulting in 162 articles. After critical reading based on titles and abstracts and following the inclusion and exclusion criteria, 26 articles were included. In the articles, women over 40 years old, smokers and nonsmokers, mainly constituted the analyzed groups. Eight studies broached the epidemiological relationship with PD and RA. Four trials demonstrated that the periodontal treatment influenced the severity of RA and periodontal clinical parameters. Nine studies were related with bacteria influence in the pathogenesis of RA and the presence of citrullinated proteins, autoantibodies, or rheumatoid factor in patients with PD and RA. Five studies investigated the presence of mediators of inflammation in PD and RA. In summary, the majority of the articles have confirmed that there is a correlation between PD and RA, since both disorders have characteristics in common and result from an imbalance in the immunoinflammatory response. Vilana Maria Adriano Araújo, Iracema Matos Melo, and Vilma Lima Copyright © 2015 Vilana Maria Adriano Araújo et al. All rights reserved. The X-Linked Inhibitor of Apoptosis Protein Inhibitor Embelin Suppresses Inflammation and Bone Erosion in Collagen Antibody Induced Arthritis Mice Tue, 04 Aug 2015 10:35:06 +0000 Objective. To investigate the effect of Embelin, an inhibitor of X-Linked Inhibitor of Apoptosis Protein (XIAP), on inflammation and bone erosion in a collagen antibody induced arthritis (CAIA) in mice. Methods. Four groups of mice ( per group) were allocated: CAIA untreated mice, CAIA treated with Prednisolone (10 mg/kg/day), CAIA treated with low dose Embelin (30 mg/kg/day), and CAIA treated with high dose Embelin (50 mg/kg/day). Joint inflammation was evaluated using clinical paw score and histological assessments. Bone erosion was assessed using micro-CT, tartrate resistant acid phosphatase (TRAP) staining, and serum carboxy-terminal collagen crosslinks (CTX-1) ELISA. Immunohistochemistry was used to detect XIAP protein. TUNEL was performed to identify apoptotic cells. Results. Low dose, but not high dose Embelin, suppressed inflammation as reflected by lower paw scores () and lower histological scores for inflammation. Low dose Embelin reduced serum CTX-1 () and demonstrated lower histological score and TRAP counting, and slightly higher bone volume as compared to CAIA untreated mice. XIAP expression was not reduced but TUNEL positive cells were more abundant in Embelin treated CAIA mice. Conclusion. Low dose Embelin suppressed inflammation and serum CTX-1 in CAIA mice, indicating a potential use for Embelin to treat pathological bone loss. Anak A. S. S. K. Dharmapatni, Melissa D. Cantley, Victor Marino, Egon Perilli, Tania N. Crotti, Malcolm D. Smith, and David R. Haynes Copyright © 2015 Anak A. S. S. K. Dharmapatni et al. All rights reserved. Inflammatory Mediators of Leprosy Reactional Episodes and Dental Infections: A Systematic Review Mon, 03 Aug 2015 14:35:33 +0000 Reactional episodes in leprosy are a result of complex interactions between the immune system, Mycobacterium leprae, and predisposing factors, including dental infections. To determine the main inflammatory mediators in the immunopathological process of dental infections and leprosy reactions, we conducted a systematic review of primary literature published between 1996 and 2013. A three-stage literature search was performed (Stage I, “leprosy reactions” and “inflammatory mediators”; Stage II, “dental infections” and “inflammatory mediators”; and Stage III, “leprosy reactions,” “dental infections,” and “inflammatory mediators”). Of the 911 eligible publications, 10 were selected in Stage I, 68 in Stage II, and 1 in Stage III. Of the 27 studied inflammatory mediators, the main proinflammatory mediators were IL-6, IFN-γ, TNF-α, IL-1β, and IL-17; the main anti-inflammatory mediators were IL-10 and IL-4. Serum IL-6 and TNF-α concentrations were significant during periodontal and reactional lesion evolution; IFN-γ and IL-1β were associated with types 1 and 2 reactions and chronic periodontal disease. The proinflammatory mediators in dental infections and leprosy reactions, especially IL-6 and TNF-α, were similar across studies, regardless of the laboratory technique and sample type. IFN-γ and IL-1β were significant for leprosy reactions and periodontal diseases. This pattern was maintained in serum. D. C. B. Cortela, A. L. de Souza Junior, M. C. L. Virmond, and E. Ignotti Copyright © 2015 D. C. B. Cortela et al. All rights reserved. The Influence of Interleukin 17A and IL17F Polymorphisms on Chronic Periodontitis Disease in Brazilian Patients Mon, 03 Aug 2015 13:50:26 +0000 A case-control study was conducted on patients with chronic periodontitis (CP) and healthy controls with the aim of evaluating possible association between interleukin 17A (IL17A) G197A (rs2275913) and IL17F T7488C (rs763780) polymorphisms and periodontitis. Genotypes were determined by PCR-RFLP method. Statistical analyses were conducted using the OpenEpi and SNPStas software to calculate Chi-square with Yates correction or Fisher’s exact tests, odds ratios (OR), and 95% confidence intervals (CIs). SNPStas software was used to calculate Hardy-Weinberg equilibrium. IL17A AA genotype was more frequent in patients with chronic periodontitis (CP) in the codominant and recessive models (; OR = 2.53 and ; OR = 2.46, resp.), the females with CP (, OR = 4.34), Caucasoid patients with CP (, OR = 3.45), and nonsmoking Caucasian patients with CP (, OR = 3.51). The IL17A A allele was also more frequent in Caucasians with CP (, OR = 1.59). IL17F T7488C polymorphism was not associated with chronic periodontitis. In these patients from Southern Brazil, the IL17A rs2275913 polymorphisms, IL17A AA genotype, and the A allele were associated with a susceptibility to chronic periodontitis. Joana Maira Valentini Zacarias, Emília Ângela Sippert, Patrícia Yumeko Tsuneto, Jeane Eliete Laguila Visentainer, Cléverson de Oliveira e Silva, and Ana Maria Sell Copyright © 2015 Joana Maira Valentini Zacarias et al. All rights reserved. The Two-Way Association of Periodontal Infection with Systemic Disorders: An Overview Mon, 03 Aug 2015 13:46:33 +0000 Oral cavity that harbors diverse bacterial populations could also act as a site of origin for spread of pathogenic microorganisms to different body sites, particularly in immunocompromised hosts, patients, the elderly, or the underprivileged. A number of recent publications have advocated that patients with periodontal diseases are more susceptible to metabolic endotoxemia, inflammation, obesity, type 2 diabetes, and other related systemic complications, concluding that periodontal diseases could be a potential contributing risk factor for a wide array of clinically important systemic diseases. However, despite a significant increase in the prevalence of periodontal infections and systemic diseases in the past few decades, the fundamental biological mechanisms of connection between these ailments are still not fully explicated. Consequently, the mechanisms by which this bidirectional damage occurs are being explored with a concentric vision to develop strategies that could prevent or control the complications of these ailments. This paper attempts to summarize and hypothesize the diverse mechanisms that hint to a certain connection between the two prevalent chronic situations. Ravinder Nagpal, Yuichiro Yamashiro, and Yuichi Izumi Copyright © 2015 Ravinder Nagpal et al. All rights reserved. HLA Haplotypes and Genotypes Frequencies in Brazilian Chronic Periodontitis Patients Mon, 03 Aug 2015 13:29:01 +0000 Human leukocyte antigens (HLA) have a pivotal role in immune response and may be involved in antigen recognition of periodontal pathogens. However, the associations of HLA with chronic periodontitis (CP) have not been previously studied in the Brazilian population. In an attempt to clarify the issue of genetic predisposition to CP, we examined the distribution of HLA alleles, genotypes, and haplotypes in patients from Southern Brazil. One hundred and eight CP patients and 151 healthy and unrelated controls with age-, gender-, and ethnicity-matched were HLA investigated by polymerase chain reaction with sequence specific oligonucleotides. To exclude smoking as a predisposing factor, statistical analyses were performed in the total sample and in nonsmoking individuals. The significant results showed a positive association of the A∗02/HLA-B∗40 haplotype with CP (total samples: 4.2% versus 0%, = 0.03; nonsmokers: 4.3% versus 0%, = 0.23) and a lower frequency of HLA-B∗15/HLA-DRB1∗11 haplotype in CP compared to controls (total samples: 0.0% versus 4.3%, = 0.04; nonsmokers: 0 versus 5.1%, = 1.0). In conclusion, the HLA-A∗02/B∗40 haplotype may contribute to the development of CP, while HLA-B∗15/DRB1∗11 haplotype might indicate resistance to disease among Brazilians. Emília Ângela Sippert, Cléverson de Oliveira e Silva, Christiane Maria Ayo, Silvia Barbosa Dutra Marques, Jeane Eliete Laguila Visentainer, and Ana Maria Sell Copyright © 2015 Emília Ângela Sippert et al. All rights reserved. Inflammatory Bowel Disease: An Overview of Immune Mechanisms and Biological Treatments Mon, 03 Aug 2015 12:20:19 +0000 Inflammatory bowel diseases (IBD) are characterized by chronic inflammation of the intestinal tract associated with an imbalance of the intestinal microbiota. Crohn’s disease (CD) and ulcerative colitis (UC) are the most widely known types of IBD and have been the focus of attention due to their increasing incidence. Recent studies have pointed out genes associated with IBD susceptibility that, together with environment factors, may contribute to the outcome of the disease. In ulcerative colitis, there are several therapies available, depending on the stage of the disease. Aminosalicylates, corticosteroids, and cyclosporine are used to treat mild, moderate, and severe disease, respectively. In Crohn’s disease, drug choices are dependent on both location and behavior of the disease. Nowadays, advances in treatments for IBD have included biological therapies, based mainly on monoclonal antibodies or fusion proteins, such as anti-TNF drugs. Notwithstanding the high cost involved, these biological therapies show a high index of remission, enabling a significant reduction in cases of surgery and hospitalization. Furthermore, migration inhibitors and new cytokine blockers are also a promising alternative for treating patients with IBD. In this review, an analysis of literature data on biological treatments for IBD is approached, with the main focus on therapies based on emerging recombinant biomolecules. Bruno Rafael Ramos de Mattos, Maellin Pereira Gracindo Garcia, Julia Bier Nogueira, Lisiery Negrini Paiatto, Cassia Galdino Albuquerque, Caique Lopes Souza, Luís Gustavo Romani Fernandes, Wirla Maria da Silva Cunha Tamashiro, and Patricia Ucelli Simioni Copyright © 2015 Bruno Rafael Ramos de Mattos et al. All rights reserved. Response to Infliximab in Crohn’s Disease: Genetic Analysis Supporting Expression Profile Mon, 03 Aug 2015 12:05:19 +0000 Substantial proportion of Crohn’s disease (CD) patients shows no response or a limited response to treatment with infliximab (IFX) and to identify biomarkers of response would be of great clinical and economic benefit. The expression profile of five genes (S100A8-S100A9, G0S2, TNFAIP6, and IL11) reportedly predicted response to IFX and we aimed at investigating their etiologic role through genetic association analysis. Patients with active CD (350) who received at least three induction doses of IFX were included and classified according to IFX response. A tagging strategy was used to select genetic polymorphisms that cover the variability present in the chromosomal regions encoding the identified genes with altered expression. Following genotyping, differences between responders and nonresponders to IFX were observed in haplotypes of the studied regions: S100A8-S100A9 (rs11205276G/rs3014866C/rs724781C/rs3006488A; ); G0S2 (rs4844486A/rs1473683T; ); TNFAIP6 (rs11677200C/rs2342910A/rs3755480G/rs10432475A; ); and IL11 (rs1126760C/rs1042506G; ). These differences were amplified in patients with colonic and ileocolonic location for all but the TNFAIP6 haplotype, which evidenced significant difference in ileal CD patients. Our results support the role of the reported expression signature as predictive of anti-TNF outcome in CD patients and suggest an etiological role of those top-five genes in the IFX response pathway. Luz María Medrano, Carlos Taxonera, Cristina González-Artacho, Virginia Pascual, María Gómez-García, Manuel Barreiro-de Acosta, José L. Pérez-Calle, Fernando Bermejo, Antonio López-Sanromán, Dolores Martín Arranz, Javier P. Gisbert, Juan Luis Mendoza, Javier Martín, Concepción Núñez, and Elena Urcelay Copyright © 2015 Luz María Medrano et al. All rights reserved. Systemic Autoimmune, Rheumatic Diseases and Coinciding Psoriasis: Data from a Large Single-Centre Registry and Review of the Literature Mon, 03 Aug 2015 11:50:43 +0000 Psoriasis is a systemic immune-inflammatory disease characterized by chronic or recurrent skin symptoms, psoriatic arthritis, enthesopathy, and uveitis. Psoriasis has recently been published to appear with various autoimmune disorders, but the coexistence has been systematically reviewed by only few studies until now. In the present study, charts and electronic database of 4344 patients with various systemic autoimmune disorders, under regular medical control at our department, were reviewed retrospectively searching for association with psoriasis. Hereby, we demonstrate 25 psoriatic patients coinciding with various systemic autoimmune diseases. The coexistence of psoriasis and autoimmune diseases resulted in the worsening of the clinical outcome of the autoimmune diseases as indicated by higher frequency and dosages of glucocorticoid use, need for biologicals, and other comorbidities. These results suggest common environmental and genetic background as well as therapeutic possibilities in the future. Anna Bazsó, Péter Szodoray, Ágnes Szappanos, Judit Korda, Patrícia Pálfi, Emese Kiss, and Gyula Poór Copyright © 2015 Anna Bazsó et al. All rights reserved. The Emerging and Diverse Roles of Src-Like Adaptor Proteins in Health and Disease Mon, 03 Aug 2015 11:26:28 +0000 Although Src-like adaptor proteins (SLAP-1 and SLAP-2) were mainly studied in lymphocytes, where they act as negative regulators and provide fine control of receptor signaling, recently, several other functions of these proteins were discovered. In addition to the well-characterized immunoregulatory functions, SLAP proteins appear to have an essential role in the pathogenesis of type I hypersensitivity, osteoporosis, and numerous malignant diseases. Both adaptor proteins are expressed in a wide variety of tissues, where they have mostly inhibitory effects on multiple intracellular signaling pathways. In this review, we summarize the diverse effects of SLAP proteins. Nikolett Marton, Eszter Baricza, Barbara Érsek, Edit I. Buzás, and György Nagy Copyright © 2015 Nikolett Marton et al. All rights reserved. The Role of Poly(ADP-ribose) Polymerase-1 in Rheumatoid Arthritis Mon, 03 Aug 2015 11:09:43 +0000 Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme with a crucial role in the maintenance of genomic stability. In addition to the role of PARP-1 in DNA repair, multiple studies have also demonstrated its involvement in several inflammatory diseases, such as septic shock, asthma, atherosclerosis, and stroke, as well as in cancer. In these diseases, the pharmacological inhibition of PARP-1 has shown a beneficial effect, suggesting that PARP-1 regulates their inflammatory processes. In recent years, we have studied the role of PARP-1 in rheumatoid arthritis, as have other researchers, and the results have shown that PARP-1 has an important function in the development of this disease. This review summarizes current knowledge on the effects of PARP-1 in rheumatoid arthritis. Samuel García and Carmen Conde Copyright © 2015 Samuel García and Carmen Conde. All rights reserved.