Molecular Characterization of the NLRC4 Expression in Relation to Interleukin-18 Levels.
نویسندگان
چکیده
BACKGROUND Interleukin-18 (IL-18) is a pleiotropic cytokine centrally involved in the cytokine cascade with complex immunomodulatory functions in innate and acquired immunity. Circulating IL-18 concentrations are associated with type 2 diabetes mellitus, cardiovascular events, and diverse inflammatory and autoimmune disorders. METHODS AND RESULTS To identify causal variants affecting circulating IL-18 concentrations, we applied various omics and molecular biology approaches. By genome-wide association study, we confirmed association of IL-18 levels with a single nucleotide polymorphism in the untranslated exon 2 of the inflammasome component NLRC4 (NLR family, caspase recruitment domain-containing 4) gene on chromosome 2 (rs385076; P=2.4 × 10(-45)). Subsequent molecular analyses by gene expression analysis and reporter gene assays indicated an effect of rs385076 on NLRC4 expression and differential isoform usage by modulating binding of the transcription factor PU.1. CONCLUSIONS Our study provides evidence for the functional causality of single nucleotide polymorphism rs385076 within the NLRC4 gene in relation to IL-18 activation.
منابع مشابه
Effect of Cyperus Rotundus on Cytokine Gene Expression in Experimental Inflammatory Bowel Disease
Background: The protective effect of the chloroform extract of Cyperus rotundus (CHCR) is attributed to its anti-inflammatory and antioxidant activities. Cytokines, important regulators of inflammation and repair, play a key role in the pathogenesis of inflammatory bowel disease (IBD). Targeting these cytokines can effectively ameliorate the symptoms of IBD. The aim of the present study was to ...
متن کاملRole of Propolis as a pharmaceutical candidate on interleukin-1β proinflammatory cytokine expression in Alzheimer's rat
Background: One of the important factors that play a key role in the pathogenesis of Alzheimer's disease (AD) is inflammatory processes leading to impaired expression of inflammatory cytokines such as interleukin-6, TNF-α, and interleukin-1β (IL-1β). Propolis, as a therapeutic compound, has anti-inflammatory and antioxidant properties. Therefore, the aim of the present study was to investigate ...
متن کاملAssociation between Helicobacter pylori cagA, babA2 Virulence Factors and Gastric Mucosal Interleukin-33 mRNA Expression and Clinical Outcomes in Dyspeptic Patients
Helicobacter pylori (H. pylori) infection has been reported in more than half of the world human population. It is associated with gastric inflammation and noticeable infiltration of the immune cells to the stomach mucosa by several cytokines secretion. IL-1&beta, IL-18 have been shown to contribute to H. pylori induced gastritis, but the details of inflammation and association of virulence fac...
متن کاملInterleukin-17 Gene Expression and Serum Levels in Acute Rejected and non-Rejected Liver Transplant Patients
Background: Interleukin-17 (IL-17), as a potent proinflammatory cytokine, has a critical role in post liver transplant outcomes. However, there is not much information about the effects of IL-17 cytokine on acute liver rejection. Objective: To evaluate the role of IL-17 in post-liver transplant acute rejection. Methods: Ninety seven adult liver transplant patients who enrolled in this cross sec...
متن کاملAlcohol-Induced Liver Injury Is Modulated by Nlrp3 and Nlrc4 Inflammasomes in Mice
Alcoholic liver disease (ALD) is characterized by increased hepatic lipid accumulation (steatosis) and inflammation with increased expression of proinflammatory cytokines. Two of these cytokines, interleukin-1 β (IL-1 β ) and IL-18, require activation of caspase-1 via members of the NOD-like receptor (NLR) family. These NLRs form an inflammasome that is activated by pathogens and signals releas...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Circulation. Cardiovascular genetics
دوره 8 5 شماره
صفحات -
تاریخ انتشار 2015