International Journal of Inflammation https://www.hindawi.com The latest articles from Hindawi © 2017 , Hindawi Limited . All rights reserved. Alleviating Promotion of Inflammation and Cancer Induced by Nonsteroidal Anti-Inflammatory Drugs Wed, 10 May 2017 06:31:39 +0000 http://www.hindawi.com/journals/iji/2017/9632018/ Clinical Relevance. Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) including aspirin are of intensive use nowadays. These drugs exert their activity via the metabolism of arachidonic acid (AA) by cyclooxygenase inhibition. Though beneficial for health in some instances, both unspecific and specific cyclooxygenase inhibitor activity interfere with AA metabolism producing also proinflammatory lipids that may promote cancer. Materials and Methods. This review is based on available literature on clinical uses, biochemical investigations, molecular medicine, pharmacology, toxicity, and epidemiology-clinical studies on NSAIDs and other drugs that may be used accordingly, which was collected from electronic (SciFinder, Medline, Science Direct, and ACS among others) and library searches of books and journals. Results. Relevant literature supports the notion that NDSAID use may also promote proinflammatory biochemical events that are also related to precancerous predisposition. Several agents are proposed that may be employed in immediate future to supplement and optimize treatment with NSAIDs. In this way serious side effects arising from promotion of inflammation and cancer, especially in chronic NSAID users and high risk groups of patients, could be avoided. Anthony M. Kyriakopoulos, Markus Nagl, Stella Baliou, and Vasilleios Zoumpourlis Copyright © 2017 Anthony M. Kyriakopoulos et al. All rights reserved. The Role of Toll-Like Receptors in Autoimmune Diseases through Failure of the Self-Recognition Mechanism Wed, 03 May 2017 08:39:44 +0000 http://www.hindawi.com/journals/iji/2017/8391230/ Toll-like receptors (TLRs), part of the innate immune system that recognises molecular signatures, are important in the recognition of pathogenic components. However, when specific cellular contexts develop in which TLRs are inappropriately activated by self-components, this may lead to sterile inflammation and result in the occurrence of autoimmunity. This review analyses the available data regarding TLR biochemistry, the specific mechanisms which are brought about by TLR activation, and the importance of these mechanisms in the light of any existing and potential therapies in the field of autoimmunity. Mark Farrugia and Byron Baron Copyright © 2017 Mark Farrugia and Byron Baron. All rights reserved. Mycobacterium avium Subsp. paratuberculosis Induces Specific IgE Production in Japanese People with Allergies Mon, 24 Apr 2017 00:00:00 +0000 http://www.hindawi.com/journals/iji/2017/7959154/ Background. The prevalence of allergies is steadily increasing worldwide; however, the pathogenesis is still unclear. We hypothesized that Mycobacterium avium subsp. paratuberculosis (MAP) may contribute to allergy development. This organism can be present in dairy foods, it can elicit an immunomodulatory switch from a Th1 to a Th2 response, and it has been speculated that it is linked to several human autoimmune diseases. To determine the contribution, sera from 99 individuals with various atopic disorders and 45 healthy nonallergic controls were assessed for total IgE levels and successively for MAP-specific IgE by ELISA. Results. The mean total serum IgE level in allergic patients was  IU/mL, and in the healthy controls it was  IU/mL (AUC = 0.88; ). Among the patient groups, 50 of the 99 subjects had increased IgE total level ≥ 150 IU/mL, while 49 subjects had IgE ≤ 150 IU/mL (mean level:  IU/mL versus  IU/mL; ). Additionally, 6 out of 50 subjects (12%) with IgE ≥ 150 IU/mL and none (0%) with IgE ≤ 150 IU/mL were positive for specific MAP IgE (AUC = 0.63; ). Conclusion. The present study revealed that MAP has the ability to induce specific IgE and might contribute to the induction of allergic inflammation in genetically predisposed individuals. D. Cossu, S. Otsubo, Y. Otsubo, S. Eda, T. Suzuki, Y. Iwao, T. Kuribayashi, S. Yamamoto, L. A. Sechi, and E. Momotani Copyright © 2017 D. Cossu et al. All rights reserved. Identification of a Novel Alternatively Spliced Form of Inflammatory Regulator SWAP-70-Like Adapter of T Cells Mon, 24 Apr 2017 00:00:00 +0000 http://www.hindawi.com/journals/iji/2017/1324735/ Activation of naive CD4+ T cells results in the development of several distinct subsets of effector Th cells, including Th2 cells that play a pivotal role in allergic inflammation and helminthic infections. SWAP-70-like adapter of T cells (SLAT), also known as Def6 or IBP, is a guanine nucleotide exchange factor for small GTPases, which regulates CD4+ T cell inflammatory responses by controlling Ca2+/NFAT signaling. In this study, we have identified a novel alternatively spliced isoform of SLAT, named SLAT2, which lacks the region encoded by exons 2–7 of the Def6 gene. SLAT2 was selectively expressed in differentiated Th2 cells after the second round of in vitro stimulation, but not in differentiated Th1, Th17, or regulatory T (Treg) cells. Functional assays revealed that SLAT2 shared with SLAT the ability to enhance T cell receptor- (TCR-) mediated activation of NFAT and production of IL-4 but was unable to enhance TCR-induced adhesion to ICAM-1. Ectopic expression of SLAT2 or SLAT in Jurkat T cells resulted in the expression of distinct forms of filopodia, namely, short versus long ones, respectively. These results demonstrate that modulating either SLAT2 or SLAT protein expression could play critical roles in cytokine production and actin reorganization during inflammatory immune responses. Marie Hashimoto, Jun-ichi Nagao, Shojiro Ikezaki, Sonoko Tasaki, Ken-ichi Arita-Morioka, Yuka Narita, Tamaki Cho, Kenji Yuasa, Amnon Altman, and Yoshihiko Tanaka Copyright © 2017 Marie Hashimoto et al. All rights reserved. The Level of Oxidative Neutrophil Response When Determining Endotoxin Activity Assay: A New Biomarker for Defining the Indications and Effectiveness of Intensive Care in Patients with Sepsis Wed, 12 Apr 2017 09:56:55 +0000 http://www.hindawi.com/journals/iji/2017/3495293/ Background. To analyse the clinical informativity of the neutrophil oxidative response level (“Response”) during an Endotoxin Activity Assay (EAA) as a new biomarker defining the indications and effectiveness of intensive care in cardiac surgical patients with septic complications. Methods. Blood samples were taken from 198 adult patients who were admitted to the ICU after cardiac surgery (SIRS: 34, MODS: 36, and sepsis: 128). The composite of laboratory studies included CRP, PCT, EAA with “Response” level, and presepsin. Results. 83% of patients had a “normal” neutrophil response, 12% of patients had a low neutrophil response, and 5% of patients had a critically low neutrophil response. Patients with critically low responses had the lowest values of the EAA and the highest concentrations of PSP and D-dimer (). Conclusions. EAA results should be interpreted with the level of neutrophil response. “Response” > 0.5 has a negative predictive value; the EAA < 0.6 at “Response” < 0.5 may indicate a high level of endotoxaemia. Michael Yaroustovsky, Ekaterina Rogalskaya, Marina Plyushch, Ludmila Klimovich, Nataliya Samsonova, and Marina Abramyan Copyright © 2017 Michael Yaroustovsky et al. All rights reserved. Curcumin Inhibits NTHi-Induced MUC5AC Mucin Overproduction in Otitis Media via Upregulation of MAPK Phosphatase MKP-1 Wed, 12 Apr 2017 07:35:01 +0000 http://www.hindawi.com/journals/iji/2017/4525309/ Otitis media (OM), characterized by the presence of mucus overproduction and excess inflammation in the middle ear, is the most common childhood infection. Nontypeable Haemophilus influenzae (NTHi) pathogen is responsible for approximately one-third of episodes of bacteria-caused OM. Current treatments for bacterial OM rely on the systemic use of antibiotics, which often leads to the emergence of multidrug resistant bacterial strains. Therefore there is an urgent need for developing alternative therapies strategies for controlling mucus overproduction in OM. MUC5AC mucin has been shown to play a critical role in the pathogenesis of OM. Here we show that curcumin derived from Curcuma longa plant is a potent inhibitor of NTHi-induced MUC5AC mucin expression in middle ear epithelial cells. Curcumin inhibited MUC5AC expression by suppressing activation of p38 MAPK by upregulating MAPK phosphatase MKP-1. Thus, our study identified curcumin as a potential therapeutic for inhibiting mucin overproduction in OM by upregulating MKP-1, a known negative regulator of inflammation. Anuhya Sharma Konduru, Shingo Matsuyama, Byung-Cheol Lee, Kensei Komatsu, and Jian-Dong Li Copyright © 2017 Anuhya Sharma Konduru et al. All rights reserved. High-Sensitive C-Reactive Protein Levels in a Group of Syrian University Male Students and Its Associations with Smoking, Physical Activity, Anthropometric Measurements, and Some Hematologic Inflammation Biomarkers Mon, 10 Apr 2017 07:39:38 +0000 http://www.hindawi.com/journals/iji/2017/7326527/ In Syria, health risk data on young males are limited. Hence, the aim of the present study was to evaluate cardiovascular disease (CVD) risk factors along with C-reactive protein levels measured by high-sensitive method (hsCRP) in a group of healthy males of university students (, 18–25 years old). Participants’ anthropometric characteristics; alcohol drinking, smoking, and physical activity habits; parents medical history; and some inflammatory biomarkers were inspected for their associations with hsCRP. Results. Regarding hsCRP level, 19 participants were at average (1–3 mg/L) and 13 were at high (>3 mg/L) risk of CVD. Nonparametric statistical tests ( value < 0.05) revealed that hsCRP level was higher in participants who had high body mass index (BMI), had high BMI with high waist-to-hip ratio (WHR), or did not practice sport frequently. Unexpectedly, it did not vary between smokers and nonsmokers. In general, it correlated positively with anthropometric and erythrocyte sedimentation rate (ESR) measurements. Nevertheless, it negatively correlated with sports practicing in overall and nonsmoker groups and in participants whose parents were without medical history. Finally, when participants with high BMI were smokers, did not practice sport frequently, or had a parent with medical history, their hsCRP levels were higher than others who had the same circumstances but with low BMI. Wafika Zarzour, Nada Dehneh, and Mazen Rajab Copyright © 2017 Wafika Zarzour et al. All rights reserved. Transcriptional and Molecular Pathways Activated in Mesenteric Adipose Tissue and Intestinal Mucosa of Crohn’s Disease Patients Sun, 09 Apr 2017 00:00:00 +0000 http://www.hindawi.com/journals/iji/2017/7646859/ Crohn’s disease (CD) is a chronic inflammatory disorder, characterized by cytokine imbalance and transcription signaling pathways activation. In addition, the increase of mesenteric adipose tissue (MAT) near the affected intestinal area is a hallmark of CD. Therefore, we evaluated the transcription signaling pathways and cytokines expression in intestinal mucosa and MAT of active CD patients. Ten patients with ileocecal CD and eight with noninflammatory diseases were studied. The biopsies of intestinal mucosa and MAT were snap-frozen and protein expression was determined by immunoblotting. RNA levels were measured by qPCR. The pIkB/IkB ratio and TNFα level were significantly higher in intestinal mucosa of CD when compared to controls. However, STAT1 expression was similar between intestinal mucosa of CD and controls. Considering the MAT, the pIkB/IkB ratio was significantly lower and the anti-inflammatory cytokine IL10 was significantly higher in CD when compared to controls. Finally, the protein content of pSTAT1 was higher in MAT of CD compared to controls. These findings reinforce the predominance of the proinflammatory NF-kB pathway in CD intestinal mucosa. For the first time, we showed the activation of STAT1 pathway in MAT of CD patients, which may help to understand the physiopathology of this immune mediated disease. Andressa Coope, Lívia Bitencourt Pascoal, Francesca Aparecida Ramos da Silva, José Diego Botezelli, Maria de Lourdes Setsuko Ayrizono, Marciane Milanski, Michel Gardere Camargo, Núria Planell, Mariana Portovedo, Cilene Bicca Dias, João José Fagundes, and Raquel Franco Leal Copyright © 2017 Andressa Coope et al. All rights reserved. Cytokines as Biomarkers and Their Respective Clinical Cutoff Levels Sun, 09 Apr 2017 00:00:00 +0000 http://www.hindawi.com/journals/iji/2017/4309485/ Cytokines, including interleukins, interferons, tumor necrosis factors, and chemokines, have a variety of pro- and anti-inflammatory effects in the body through a number of biochemical pathways and interactions. Stimuli, actions, interactions, and downstream effects of cytokines have been investigated in more depth in recent years, and clinical research has also been conducted to implicate cytokines in causal patterns in certain diseases. However, particular cutoffs of cytokines as biomarkers for disease processes have not been well studied, and this warrants future work to potentially improve diagnoses for diseases with inflammatory markers. A limited number of studies in this area are reviewed, considering diseases correlated with abnormal cytokine profiles, as well as specific cutoffs at which cytokines have been deemed clinically useful for diagnosing those diseases through Receiver Operator Characteristics modeling. In light of studies such as those discussed in this review, cytokine testing has the potential to support diagnosis due to its lack of invasiveness and low cost, compared to other common types of testing for infections and inflammatory diseases. Rebecca N. Monastero and Srinivas Pentyala Copyright © 2017 Rebecca N. Monastero and Srinivas Pentyala. All rights reserved. Psoriatic Arthritis Is an Indicator of Significant Renal Damage in Patients with Psoriasis: An Observational and Epidemiological Study Wed, 22 Mar 2017 07:07:39 +0000 http://www.hindawi.com/journals/iji/2017/5217687/ Background. Psoriasis affects joints in around 30% of the patients. Recent studies have demonstrated an increased risk of essential hypertension, ischemic heart disease, and stroke in psoriatic patients. However, the prevalence of renal disease in patients with psoriasis has not been evaluated properly. Objectives. Objectives were to evaluate renal functions in patients with psoriasis and to assess any possible relationship of renal failure with psoriasis and psoriatic arthritis. Methods. In this cross-sectional study, 30 participants were recruited into the following three groups: group-A, psoriatic arthritis; group-B, psoriasis without arthritis; and group-C, healthy subjects. Renal function tests were performed for every participant of each group. The data was analyzed by using SPSS version 16. Chi-squared and one-way ANOVA tests were applied, considering a value of less than 0.05 as a standard criterion. Results. Serum creatinine, urea, and phosphate were the highest in group-A, higher in group-B, and normal in group-C, . Similarly, GFR was the lowest in group-A, lower in group-B, and normal in group-C. The difference in mean GFR values was statistically significant, , . Moreover, proteinuria (gm/day) was seen in 96.7% of the patients with psoriatic arthritis, (, ) against 10% of the psoriatic patients without arthritis (, ). Conclusion. Derangement of renal function is more prevalent in psoriatic patients, especially in those with concomitant psoriatic arthritis. Therefore, each psoriatic patient must be routinely screened for an underlying renal failure. Abidullah Khan, Iqbal Haider, Maimoona Ayub, and Mohammad Humayun Copyright © 2017 Abidullah Khan et al. All rights reserved. HMGB1 and Histones Play a Significant Role in Inducing Systemic Inflammation and Multiple Organ Dysfunctions in Severe Acute Pancreatitis Tue, 21 Feb 2017 08:44:52 +0000 http://www.hindawi.com/journals/iji/2017/1817564/ Severe acute pancreatitis (SAP) starts as a local inflammation of pancreatic tissue that induces the development of multiple extrapancreatic organs dysfunction; however, the underlying mechanisms are still not clear. Ischemia-reperfusion, circulating inflammatory cytokines, and possible bile cytokines significantly contribute to gut mucosal injury and intestinal bacterial translocation (BT) during SAP. Circulating HMGB1 level is significantly increased in SAP patients and HMGB1 is an important factor that mediates (at least partly) gut BT during SAP. Gut BT plays a critical role in triggering/inducing systemic inflammation/sepsis in critical illness, and profound systemic inflammatory response syndrome (SIRS) can lead to multiple organ dysfunction syndrome (MODS) during SAP, and systemic inflammation with multiorgan dysfunction is the cause of death in experimental SAP. Therefore, HMGB1 is an important factor that links gut BT and systemic inflammation. Furthermore, HMGB1 significantly contributes to multiple organ injuries. The SAP patients also have significantly increased circulating histones and cell-free DNAs levels, which can reflect the disease severity and contribute to multiple organ injuries in SAP. Hepatic Kupffer cells (KCs) are the predominant source of circulating inflammatory cytokines in SAP, and new evidence indicates that hepatocyte is another important source of circulating HMGB1 in SAP; therefore, treating the liver injury is important in SAP. Runkuan Yang, Jyrki Tenhunen, and Tor Inge Tonnessen Copyright © 2017 Runkuan Yang et al. All rights reserved. Sterile Neuroinflammation and Strategies for Therapeutic Intervention Tue, 03 Jan 2017 11:44:29 +0000 http://www.hindawi.com/journals/iji/2017/8385961/ Sterile neuroinflammation is essential for the proper brain development and tissue repair. However, uncontrolled neuroinflammation plays a major role in the pathogenesis of various disease processes. The endogenous intracellular molecules so called damage-associated molecular patterns or alarmins or damage signals that are released by activated or necrotic cells are thought to play a crucial role in initiating an immune response. Sterile inflammatory response that occurs in Alzheimer’s disease (AD), Parkinson’s disease (PD), stroke, hemorrhage, epilepsy, or traumatic brain injury (TBI) creates a vicious cycle of unrestrained inflammation, driving progressive neurodegeneration. Neuroinflammation is a key mechanism in the progression (e.g., AD and PD) or secondary injury development (e.g., stroke, hemorrhage, stress, and TBI) of multiple brain conditions. Hence, it provides an opportunity for the therapeutic intervention to prevent progressive tissue damage and loss of function. The key for developing anti-neuroinflammatory treatment is to minimize the detrimental and neurotoxic effects of inflammation while promoting the beneficial and neurotropic effects, thereby creating ideal conditions for regeneration and repair. This review outlines how inflammation is involved in the pathogenesis of major nonpathogenic neuroinflammatory conditions and discusses the complex response of glial cells to damage signals. In addition, emerging experimental anti-neuroinflammatory drug treatment strategies are discussed. Manoj Banjara and Chaitali Ghosh Copyright © 2017 Manoj Banjara and Chaitali Ghosh. All rights reserved. Are Systematic Screening for Vitamin D Deficiency and Vitamin D Supplementation Currently Feasible for Ankylosing Spondylitis Patients? Mon, 02 Jan 2017 06:54:36 +0000 http://www.hindawi.com/journals/iji/2017/7840150/ Beyond its role in calcium and phosphorus metabolism for healthy bone mineralization, there is increasing awareness for vitamin D contribution in modulation of immune reactions. Given that ankylosing spondylitis (AS) is a chronic inflammatory disease involving excess immune/inflammatory activity and posing great therapeutic challenges, it is conceivable to claim that vitamin D treatment may be a safe and effective treatment to influence or modify the primary disease and its related comorbidities. Nevertheless, consistent body of research supporting this hypothesis is still lacking. In this paper, we examine whether systematic screening and treatment for vitamin D deficiency are feasible at present. We will review the immunomodulatory role of vitamin D and its contribution in initiation and progression of AS, as well as how they would determine the occurrence of comorbid conditions. Our conclusion is that despite the overwhelmed interest about vitamin D treatment in AS patients, systematic screening and treatment for vitamin D deficiency of all AS patients are not feasible as yet. This stresses the need for further extensive well-designed research to prove vitamin D efficacy in AS beyond bone protection. And if utility is proven, personalized treatment regimes, duration of treatment, and threshold values for vitamin D should be provided. Mickael Essouma and Jean Jacques N. Noubiap Copyright © 2017 Mickael Essouma and Jean Jacques N. Noubiap. All rights reserved. Hyperexcitability in Spinal WDR Neurons following Experimental Disc Herniation Is Associated with Upregulation of Fractalkine and Its Receptor in Nucleus Pulposus and the Dorsal Root Ganglion Mon, 26 Dec 2016 12:57:15 +0000 http://www.hindawi.com/journals/iji/2016/6519408/ Introduction. Lumbar radicular pain following intervertebral disc herniation may be associated with a local inflammatory response induced by nucleus pulposus (NP) cells. Methods. In anaesthetized Lewis rats, extracellular single unit recordings of wide dynamic range (WDR) neurons in the dorsal horn and qPCR were used to explore the effect of NP application onto the dorsal nerve roots (L3–L5). Results. A clear increase in C-fiber response was observed following NP conditioning. In the NP tissue, the expression of interleukin-1β (IL-1β), colony stimulating factor 1 (Csf1), fractalkine (CX3CL1), and the fractalkine receptor CX3CR1 was increased. Minocycline, an inhibitor of microglial activation, inhibited the increase in neuronal activity and attenuated the increase in IL-1β, Csf1, CX3L1, and CX3CR1 expression in NP tissue. In addition, the results demonstrated an increase in the expression of TNF, CX3CL1, and CX3CR1 in the dorsal root ganglions (DRGs). Conclusion. Hyperexcitability in the pain pathways and the local inflammation after disc herniation may involve upregulation of CX3CL1 signaling in both the NP and the DRG. Daniel Pitz Jacobsen, Aurora Moen, Fred Haugen, and Johannes Gjerstad Copyright © 2016 Daniel Pitz Jacobsen et al. All rights reserved. The Role of TLR2, TLR4, and TLR9 in the Pathogenesis of Atherosclerosis Tue, 04 Oct 2016 13:22:38 +0000 http://www.hindawi.com/journals/iji/2016/1532832/ Toll-like receptors (TLRs) are key players in the pathogenesis of inflammatory conditions including coronary arterial disease (CAD). They are expressed by a variety of immune cells where they recognize pathogen-associated molecular patterns (PAMPs). TLRs recruit adaptor molecules, including myeloid differentiation primary response protein (MYD88) and TIRF-related adaptor protein (TRAM), to mediate activation of MAPKs and NF-kappa B pathways. They are associated with the development of CAD through various mechanisms. TLR4 is expressed in lipid-rich and atherosclerotic plaques. In TLR2−/− and TLR4−/− mice, atherosclerosis-associated inflammation was diminished. Moreover, TLR2 and TLR4 may induce expression of Wnt5a in advanced staged atheromatous plaque leading to activation of the inflammatory processes. TLR9 is activated by CpG motifs in nucleic acids and have been implicated in macrophage activation and the uptake of oxLDL from the circulation. Furthermore, TLR9 also stimulates interferon-α (INF-α) secretion and increases cytotoxic activity of CD4+ T-cells towards coronary artery tunica media smooth muscle cells. This review outlines the pathophysiological role of TLR2, TLR4, and TLR9 in atherosclerosis, focusing on evidence from animal models of the disease. Mohsin H. K. Roshan, Amos Tambo, and Nikolai P. Pace Copyright © 2016 Mohsin H. K. Roshan et al. All rights reserved. Inflammatory Serum Protein Profiling of Patients with Lumbar Radicular Pain One Year after Disc Herniation Wed, 11 May 2016 12:15:30 +0000 http://www.hindawi.com/journals/iji/2016/3874964/ Earlier studies suggest that lumbar radicular pain following disc herniation may be associated with a local or systemic inflammatory process. In the present study, we investigated the serum inflammatory protein profile of such patients. All 45 patients were recruited from Oslo University Hospital, Ullevål, Norway, during the period 2007–2009. The new multiplex proximity extension assay (PEA) technology was used to analyze the levels of 92 proteins. Interestingly, the present data showed that patients with radicular pain 12 months after disc herniation may be different from other patients with regard to many measurable serum cytokines. Given a false discovery rate (FDR) of 0.10 and 0.05, we identified 41 and 13 proteins, respectively, which were significantly upregulated in the patients with severe pain one year after disc herniation. On the top of the list ranked by estimated increase we found C-X-C motif chemokine 5 (CXCM5; 217% increase), epidermal growth factor (EGF; 142% increase), and monocyte chemotactic protein 4 (MCP-4; 70% increase). Moreover, a clear overall difference in the serum cytokine profile between the chronic and the recovered patients was demonstrated. Thus, the present results may be important for future protein serum profiling of lumbar radicular pain patients with regard to prognosis and choice of treatment. We conclude that serum proteins may be measurable molecular markers of persistent pain after disc herniation. Aurora Moen, Anne-Li Lind, Måns Thulin, Masood Kamali-Moghaddam, Cecilie Røe, Johannes Gjerstad, and Torsten Gordh Copyright © 2016 Aurora Moen et al. All rights reserved. The Effect of Periodontitis on Expression of Interleukin-21: A Systematic Review Mon, 22 Feb 2016 13:19:46 +0000 http://www.hindawi.com/journals/iji/2016/3507503/ Purpose. Inflammation and tissue breakdown are led by an array of inflammatory destructive mediators associated with initiation and progression of inflammatory diseases like periodontitis. Current evidence shows that these inflammatory mediators have a definitive role in the pathogenesis of various systemic diseases with an inflammatory component. Interleukin-21 (IL-21) has been associated with systemic diseases like rheumatoid arthritis and Crohn’s disease that follow a chronic inflammatory cascade. Similarly recent studies have associated Interleukin-21 levels with periodontitis. This systematic review was aimed to assess the levels of IL-21 in subjects with periodontitis. Methods. A complete literature search was done in PubMed, Medline, Science Direct, and Cochrane databases and Google Scholar based on the inclusion/exclusion criteria. Six relevant articles were procured. Full text was read individually by two reviewers and data extraction was done based on STROBE statement. Results. After data extraction five observational and one interventional study were obtained. All the studies showed an increased expression of IL-21 in periodontitis and the interventional study showed reduction in IL-21 levels after nonsurgical periodontal therapy (NSP). Conclusion. Interleukin-21 levels are higher in periodontitis than controls. With this limited evidence further longitudinal studies are required to consider this as a definitive inflammatory marker. Archana Mootha, Sankari Malaiappan, N. D. Jayakumar, Sheeja S. Varghese, and Julie Toby Thomas Copyright © 2016 Archana Mootha et al. All rights reserved. Association of Alanine Aminotransferase and Periodontitis: A Cross-Sectional Analysis—NHANES 2009–2012 Thu, 11 Feb 2016 12:28:54 +0000 http://www.hindawi.com/journals/iji/2016/3901402/ Objective. Alanine Aminotransferase is an enzyme associated with not only liver diseases, liver conditions, and metabolic syndrome, but also inflammation. Periodontitis is associated with increased cytokines and other markers of inflammation. The purpose of this study is to determine if an independent association between Alanine Aminotransferase and periodontitis exists. Methods. Data from the 2009-2010 and 2011-2012 National Health and Nutrition Surveys (NHANES) were combined. Data concerning periodontitis and Alanine Aminotransferase were extracted and analyzed with Rao Scott Chi-square and logistic regressions. Serum Alanine Aminotransferase was dichotomized at 40 units/liter, and periodontitis was dichotomized to the presence or absence of periodontitis. Results. In bivariate Chi-square analyses, periodontitis and Alanine Aminotransferase were associated () and remained significant in unadjusted logistic regression (OR = 1.30 [95% CI: 1.02, 1.65]). However, when other known risk factors of periodontitis were included in the analyses, the relationship attenuated and failed to reach significance (adjusted OR = 1.17 [95% CI: 0.85, 1.60]). Conclusion. Our study adds to the literature a positive but attenuated association of serum Alanine Aminotransferase with periodontitis which failed to reach significance when other known, strong risk factors of periodontitis were included in the analysis. R. Constance Wiener, Usha Sambamoorthi, and Richard J. Jurevic Copyright © 2016 R. Constance Wiener et al. All rights reserved. The Pattern of Juvenile Idiopathic Arthritis in a Single Tertiary Center in Saudi Arabia Sun, 07 Feb 2016 11:10:32 +0000 http://www.hindawi.com/journals/iji/2016/7802957/ Introduction. Juvenile Idiopathic Arthritis (JIA) is the most common chronic arthritis in children. Our aim is to describe demographic, clinical, and laboratory characteristics and treatment of JIA patients followed up in Pediatric Rheumatology clinic in a tertiary center in Saudi Arabia. Methods. Medical records of all patients who are followed up between January 2007 and January 2015 were retrospectively reviewed. Data were collected about demographic, clinical, and laboratory features and treatment. Results. Total patients were 82, males were 31 (37.8%), and mean age of JIA onset was 7.1 ± 3.6 yr. Mean follow-up duration was 2.67±1.6 yr. Systemic onset JIA (SoJIA) was the commonest (36.5%), followed by polyarticular in 29.2% and oligoarticular in 28%. Large and small joints are involved in 76 (92%) and 30 (36.6%), respectively. Main extra-articular feature was fever in 34 (41.4%). Uveitis was diagnosed in 7 (8.5%) and in 5 (21.7%) of oligoarticular JIA. Anemia was found in 49 (59.7%), high ESR in 45 (54.8%), and leukocytosis and thrombocytosis in 33 (40.2%). Positive ANA was found in 30 (36.5%) mainly in oligoarticular subtype as 12 (52%) patients (out of 23) had this positive test. 9 patients (10.9%) required NSAIDs only, 6 patients (7.3%) required NSAIDs and intra-articular steroids only, and 19 (23%) required NSAIDs, methotrexate, steroids, and biologics. Conclusion. SoJIA is the most common JIA subtype in our study. A population based rather than a single center study will give more details about JIA characteristics in Saudi Arabia Mohammad H. Al-Hemairi, Shatha M. Albokhari, and Mohammed A. Muzaffer Copyright © 2016 Mohammad H. Al-Hemairi et al. All rights reserved. Investigation of the Anti-Inflammatory and Analgesic Activities of Ethanol Extract of Stem Bark of Sonapatha Oroxylum indicum In Vivo Tue, 26 Jan 2016 08:03:56 +0000 http://www.hindawi.com/journals/iji/2016/8247014/ Inflammation is all a pervasive phenomenon, which is elicited by the body in response to obnoxious stimuli as a protective measure. However, sustained inflammation leads to several diseases including cancer. Therefore it is necessary to neutralize inflammation. Sonapatha (Oroxylum indicum), a medicinal plant, is traditionally used as a medicine in Ayurveda and other folk systems of medicine. It is commonly used to treat inflammatory diseases including rheumatoid arthritis and asthma. Despite this fact its anti-inflammatory and analgesic effects are not evaluated scientifically. Therefore, the anti-inflammatory and analgesic activities of Sonapatha (Oroxylum indicum) were studied in Swiss albino mice by different methods. The hot plate, acetic acid, and tail immersion tests were used to evaluate the analgesic activity whereas xylene-induced ear edema and formalin induced paw edema tests were used to study the anti-inflammatory activity of Sonapatha. The administration of mice with 250 and 300 mg/kg b.wt. of O. indicum reduced pain and inflammation indicating that Sonapatha possesses analgesic and anti-inflammatory activities. The maximum analgesic and anti-inflammatory activities were observed in mice receiving 300 mg/kg b.wt. of O. indicum ethanol extract. Our study indicates that O. indicum possesses both anti-inflammatory and analgesic activities and it may be useful as an anti-inflammatory agent in the inflammation related disorders. K. Lalrinzuali, M. Vabeiryureilai, and Ganesh Chandra Jagetia Copyright © 2016 K. Lalrinzuali et al. All rights reserved. Intravenous Immunoglobulins: Mode of Action and Indications in Autoimmune and Inflammatory Dermatoses Mon, 18 Jan 2016 11:10:18 +0000 http://www.hindawi.com/journals/iji/2016/3523057/ Intravenous immunoglobulins (IVIGs), a mixture of variable amounts of proteins (albumin, IgG, IgM, IgA, and IgE antibodies), as well as salt, sugar, solvents, and detergents, are successfully used to treat a variety of dermatological disorders. For decades, IVIGs have been administered for treatment of infectious diseases and immune deficiencies, since they contain natural antibodies that represent a first-line defense against pathogens. Today their indication has expanded, including the off-label therapy for a variety of autoimmune and inflammatory diseases. In dermatology, IVIGs are administered for treatment of different disorders at different therapeutic regimens, mostly with higher doses then those administered for treatment of infectious diseases. The aim of this prospective review is to highlight the indications, effectiveness, side effects, and perspectives of the systemic treatment with IVIGs for patients with severe, life-threatening, and resistant to conventional therapies autoimmune or inflammatory dermatoses. Lyubomir A. Dourmishev, Dimitrina V. Guleva, and Ljubka G. Miteva Copyright © 2016 Lyubomir A. Dourmishev et al. All rights reserved. Nicotine Inhibits Clostridium difficile Toxin A-Induced Colitis but Not Ileitis in Rats Mon, 11 Jan 2016 07:15:35 +0000 http://www.hindawi.com/journals/iji/2016/4705065/ Nicotine is protective in ulcerative colitis but not Crohn’s disease of the small intestine, but little is known about the effects of nicotine on Clostridium difficile toxin A-induced enteritis. Isolated ileal or colonic segments in anesthetized rats were pretreated with nicotine bitartrate or other pharmacological agents before intraluminal injection of toxin A. After 3 hours, the treated segments were removed and inflammation was assessed. Nicotine biphasically inhibited toxin A colitis but not ileitis. Pretreatment with the nicotinic receptor antagonist, hexamethonium, blocked the effects of nicotine. Pretreating the colonic segments with hexamethonium before toxin A administration resulted in more inflammation than seen with toxin A alone, suggesting that a tonic nicotinic anti-inflammatory condition exists in the colon. Nicotine also inhibited toxin A-induced increased colonic concentrations of the TRPV1 (transient receptor potential vanilloid subtype 1) agonist, leukotriene B4 (LTB4), and release of the proinflammatory neuropeptide, substance P. Pretreatment with nicotine did not protect against direct TRPV1-mediated colitis caused by intraluminal capsaicin. Nicotinic cholinergic receptors tonically protect the colon against inflammation and nicotine inhibits toxin A colitis but not toxin A ileitis in rats in part by inhibition of toxin A-induced activation of TRPV1 by endogenous TRPV1 agonists such as LTB4. Steven R. Vigna Copyright © 2016 Steven R. Vigna. All rights reserved. EOLA1 Inhibits Lipopolysaccharide-Induced Vascular Cell Adhesion Molecule-1 Expression by Association with MT2A in ECV304 Cells Thu, 31 Dec 2015 13:41:07 +0000 http://www.hindawi.com/journals/iji/2015/301562/ Our research group firstly discovered endothelial-overexpressed lipopolysaccharide-associated factor 1 (EOLA1, GenBank number AY074889) as a lipopolysaccharide (LPS) responsive gene in ECV304 cells. The previous studies have further demonstrated the association of EOLA1 with metallothionein 2A (MT2A), while the role of EOLA1 during LPS-induced inflammatory response in ECV304 cells is unknown. In this report, we determined the subcellular localization of EOLA1 and the regulatory capacity of EOLA1 on vascular cell adhesion molecule-1 (VCAM-1) in response to LPS in ECV304 cells. Our results show that EOLA1 is broadly diffuse in the cells, and EOLA1 expression is dramatically induced by LPS. EOLA1 knockdown results in significant enhancement of LPS-induced VCAM-1 production. Consistent with this, overexpression of EOLA1 leads to the reduction of LPS-induced VCAM-1 production. Furthermore, MT2A knockdown reduces LPS-induced VCAM-1 production. Collectively, our results demonstrate a negative regulatory role of EOLA1 on LPS-induced VCAM-1 expression involving its association with MT2A in ECV304 cells. Weiling Leng, Xiaotian Lei, Hao Meng, Xinshou Ouyang, and Ziwen Liang Copyright © 2015 Weiling Leng et al. All rights reserved. Angiogenesis in Inflammatory Bowel Disease Tue, 29 Dec 2015 06:05:44 +0000 http://www.hindawi.com/journals/iji/2015/970890/ Angiogenesis is an important component of pathogenesis of inflammatory bowel disease (IBD). Chronic inflammation and angiogenesis are two closely related processes. Chronic intestinal inflammation is dependent on angiogenesis and this angiogenesis is modulated by immune system in IBD. Angiogenesis is a very complex process which includes multiple cell types, growth factors, cytokines, adhesion molecules, and signal transduction. Lymphangiogenesis is a new research area in the pathogenesis of IBD. While angiogenesis supports inflammation via leukocyte migration, carrying oxygen and nutrients, on the other hand, it has a major role in wound healing. Angiogenic molecules look like perfect targets for the treatment of IBD, but they have risk for serious side effects because of their nature. Canan Alkim, Huseyin Alkim, Ali Riza Koksal, Salih Boga, and Ilker Sen Copyright © 2015 Canan Alkim et al. All rights reserved. VEGFR-2 Expression in Glioblastoma Multiforme Depends on Inflammatory Tumor Microenvironment Tue, 22 Dec 2015 06:08:47 +0000 http://www.hindawi.com/journals/iji/2015/385030/ Glioblastoma multiforme (GBM) is one of the most angiogenic tumors. However, antiangiogenic therapy has not shown significant clinical efficacy. The aim of our study was to evaluate the impact of inflammatory tumor microenvironment on the expression of vascular endothelial growth factor receptor 2 (VEGFR-2). Surgically excised primary GBM tissues were histologically examined for overall extent of inflammation (score 1–3). After immunohistochemistry, the tissue expression of ICAM-1 (optical density), the number of VEGFR-2 positive (VEGFR-2+) blood vessels (per microscopic field), and the endothelial staining intensity of VEGFR-2 (score 0–3) were determined. In GBM, the extent of inflammation was 1.9 ± 0.7 (group mean ± SD). Mean optical density of inflammatory mediator ICAM-1 was 57.0 ± 27.1 (pixel values). The number of VEGFR-2+ blood vessels and endothelial VEGFR-2 staining intensity were 6.2 ± 2.4 and 1.2 ± 0.8, respectively. A positive association was found between endothelial VEGFR-2 staining intensity and the extent of inflammation (). Moreover, VEGFR-2 staining intensity correlated with the expression level of ICAM-1 (). The expression of VEGFR-2, one of the main targets of antiangiogenic therapy, depends on GBM microenvironment. Higher endothelial VEGFR-2 levels were seen in the presence of more pronounced inflammation. Target dependence on inflammatory tumor microenvironment has to be taken into consideration when treatment approaches that block VEGFR-2 signaling are designed. Jana Jaal, Marju Kase, Ave Minajeva, Mikk Saretok, Aidi Adamson, Jelizaveta Junninen, Tõnis Metsaots, Tõnu Jõgi, Madis Joonsalu, Markus Vardja, and Toomas Asser Copyright © 2015 Jana Jaal et al. All rights reserved. CCR7 Receptor Expression in Mono-MAC-1 Cells: Modulation by Liver X Receptor α Activation and Prostaglandin E2 Sun, 06 Dec 2015 13:15:07 +0000 http://www.hindawi.com/journals/iji/2015/201571/ Cell migration via chemokine receptor CCR7 expression is an essential function of the immune system. We previously showed that prostaglandin (PG), an important immunomodulatory molecule, increases CCR7 expression and function in monocytes. Here, we explore the role of the liver X receptor α (LXRα) activation on CCR7 expression in Mono-Mac-1 (MM-1) cells in the presence of PG. To do this, MM-1 cells were stimulated with the LXRα synthetic agonist T0901317 in the presence or absence of PG. CCR7 mRNA transcription was measured using quantitative RT-PCR and protein expression was examined using flow cytometry. CCR7 function was analyzed using migration assays in response to CCL19/CCL21, which are natural ligands for CCR7. Our results show that agonist-mediated activation of LXRα in the presence of PG increases CCR7 mRNA transcription and MM-1 cell migratory capacity in response to CCL19/21. In addition, our results demonstrate that engagement of the E-prostanoids 2 and 4 (E/E) receptors present on MM-1 cells is responsible for the observed increase in CCR7 mRNA expression and function during LXRα activation. Examination of monocyte migration in response to lipid derivatives such as PG and oxysterols that are produced at sites of chronic inflammation would contribute to understanding the excessive monocyte migration that characterizes atherosclerosis. Bérengère Tanné, Stéphane Bernier, and Nancy Dumais Copyright © 2015 Bérengère Tanné et al. All rights reserved. Curbing Inflammation in Multiple Sclerosis and Endometriosis: Should Mast Cells Be Targeted? Thu, 15 Oct 2015 12:33:37 +0000 http://www.hindawi.com/journals/iji/2015/452095/ Inflammatory diseases and conditions can arise due to responses to a variety of external and internal stimuli. They can occur acutely in response to some stimuli and then become chronic leading to tissue damage and loss of function. While a number of cell types can be involved, mast cells are often present and can be involved in the acute and chronic processes. Recent studies in porcine and rabbit models have supported the concept of a central role for mast cells in a “nerve-mast cell-myofibroblast axis” in some inflammatory processes leading to fibrogenic outcomes. The current review is focused on the potential of extending aspects of this paradigm into treatments for multiple sclerosis and endometriosis, diseases not usually thought of as having common features, but both are reported to have activation of mast cells involved in their respective disease processes. Based on the discussion, it is proposed that targeting mast cells in these diseases, particularly the early phases, may be a fruitful avenue to control the recurring inflammatory exacerbations of the conditions. David A. Hart Copyright © 2015 David A. Hart. All rights reserved. Lipopolysaccharide from Rhodobacter sphaeroides Attenuates Microglia-Mediated Inflammation and Phagocytosis and Directs Regulatory T Cell Response Thu, 17 Sep 2015 14:30:04 +0000 http://www.hindawi.com/journals/iji/2015/361326/ Microglia activation and neuroinflammation are key events during the progression of neurodegenerative disorders. Microglia exhibits toll-like receptors (TLRs), with predominant expression of TLR4, inducing aberrant neuroinflammation and exacerbated neurotoxicity. Studies suggest that microglia initiate infiltration of T cells into the brain that critically influence disease conditions. We report that LPS-Rs, through TLR4 antagonism, significantly inhibit TLR4 mediated inflammatory molecules like IL-1β, IL-6, TNF-α, COX-2, iNOS, and NO. LPS-Rs regulates JNK/p38 MAPKs and p65-NF-κB signaling pathways, which we report as indispensible for LPS induced neuroinflammation. LPS-Rs mitigates microglial phagocytic activity and we are first to report regulatory role of LPS-Rs which blocked microglia mediated inflammation and apoptotic cell death. LPS-Rs significantly inhibits expression of costimulatory molecules CD80, CD86, and CD40. Chemokine receptor, CCR5, and T cell recruitment chemokines, MIP-1α and CCL5, were negatively regulated by LPS-Rs. Furthermore, LPS-Rs significantly inhibited lymphocyte proliferation with skewed regulatory T (Treg) cell response as evidenced by increased FOXP3, IL-10, and TGF-β. Additionally, LPS-Rs serves to induce coordinated immunosuppressive response and confer tolerogenic potential to activated microglia extending neurosupportive microenvironment. TLR4 antagonism can be a strategy providing neuroprotection through regulation of microglia as well as the T cells. Sagar Gaikwad and Reena Agrawal-Rajput Copyright © 2015 Sagar Gaikwad and Reena Agrawal-Rajput. All rights reserved. Smoking Status Effect on Inflammatory Markers in a Randomized Trial of Current and Former Heavy Smokers Sun, 23 Aug 2015 07:41:13 +0000 http://www.hindawi.com/journals/iji/2015/439396/ Background. The level of systemic inflammation as measured by circulating levels of C-reactive protein (CRP) and interleukin-6 (IL-6) is linked to an increased risk for cardiovascular diseases (CVD) and cancer. Methods. We recruited 154 current and former smokers between 40 and 80 years of age with 25 or more pack-years of smoking history to study the relationship between inflammatory markers (CRP and IL-6) and smoking status. Results. Our results show that male smokers had significantly higher levels of serum IL-6 compared to male former smokers. We did not find any gender specific differences for smoking and CRP levels but the IL-6 levels were slightly lower in females compared to males. Additionally, our results show that CRP is significantly associated with IL-6 regardless of smoking status. Modelling indicates that the significant predictors of CRP levels were biomarkers of the metabolic syndrome while the significant predictors of IL-6 levels were age and plasma triglycerides among former smokers and the numbers of smoked packs of cigarettes per year among smokers. Conclusions. In conclusion, our study showed that CRP levels were not associated with markers of smoking intensity. However, IL-6 levels were significantly associated with smoking especially among current smokers. Sami Aldaham, Janet A. Foote, H.-H. Sherry Chow, and Iman A. Hakim Copyright © 2015 Sami Aldaham et al. All rights reserved. Curbing Inflammation in Skin Wound Healing: A Review Tue, 18 Aug 2015 05:53:08 +0000 http://www.hindawi.com/journals/iji/2015/316235/ Wound healing is a complex regulated process that results in skin scar formation in postnatal mammals. Chronic wounds are major medical problems that can confer devastating consequences. Currently, there are no treatments to prevent scarring. In the early fetus wounds heal without scarring and the healing process is characterized by relatively less inflammation compared to adults; therefore, research aimed at reducing the inflammatory process related to wound healing might speed healing and improve the final scar appearance. Rodrigo G. Rosique, Marina J. Rosique, and Jayme A. Farina Junior Copyright © 2015 Rodrigo G. Rosique et al. All rights reserved.