title: Changes in toll-like receptor (TLR)4-NFκB-IL1β signaling in male gout patients might be involved in the pathogenesis of primary gouty arthritis.
abstract: We undertook this study to determine whether the altered toll-like receptor (TLR)4-nuclear factor κB (NFκB)-interleukin1β (IL1β) signaling in peripheral blood of gout patients could provide insights into the pathogenesis of primary gouty arthritis (GA). TLR4 mRNA, TLR4 and NFκBp65 proteins expression and IL1β production were measured in 52 acute GA (AGA) and 34 non-acute GA (NAGA) male patients and 78 male healthy subjects (HC). NFκBp65 transcriptional activity and IL1β production were measured after TLR4 inhibition with anti-TLR4 antibody in peripheral whole blood from 13 AGA patients. The TLR4, NFκBp65 and IL1β expression was significantly increased in the AGA group than those in the NAGA or HC group (P < 0.05, respectively), also the levels were higher in the NAGA group comparing with those in the HC group (P < 0.05, respectively). Furthermore, moderate positive correlations were observed between concentration of uric acid and the TLR4 mRNA level, serum IL1β production (r = 0.649, 0.616), and strong positive correlation was observed between TLR4 mRNA level and serum IL1β (r = 0.848) in 52 AGA patients. On the other hand, NFκBp65 level and IL1β production were dramatically reduced after TLR4 blockade with anti-TLR4 antibody in peripheral blood from the AGA patients (P < 0.05, respectively). TLR4-NFκB-IL1β signaling might play a crucial role in the development of acute inflammation in primary gout patients.
authors.affiliation: Institute of Rheumatology and Immunology, Department of Rheumatology and Hematology, The Affiliated Hospital of North Sichuan Medical College, 63 Wenhua Road, Nanchong, 637000, Sichuan, China.
authors.forename: Yu-Feng
authors.initials: YF
authors.lastname: Qing
authors.forename: Quan-Bo
authors.initials: QB
authors.lastname: Zhang
authors.forename: Jing-Guo
authors.initials: JG
authors.lastname: Zhou
authors.forename: Li
authors.initials: L
authors.lastname: Jiang
mesh_terms: D000328:Adult; D015210:Arthritis, Gouty / Q000097:blood* / Q000175:diagnosis / Q000235:genetics / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D006073:Gout / Q000097:blood* / Q000175:diagnosis / Q000235:genetics / Q000276:immunology; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D053583:Interleukin-1beta / Q000097:blood*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000097:blood; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000097:blood* / Q000235:genetics; D051996:Transcription Factor RelA / Q000097:blood*
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D053583:Interleukin-1beta; C498143:RELA protein, human; D012333:RNA, Messenger; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051996:Transcription Factor RelA
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