BDKＲB2 + 9 /-9 基因多态性通过TLＲ-2 表达影响膝骨 关节炎中的促炎性细胞因子水平.

Objective To investigate the correlation between the bradykinin B2 receptor + 9 /-9 polymorphisms and proinflammatory cytokine levels in osteoarthritis ( OA) and the molecular mechanisms involved． Methods A total of 156 patients with primary knee OA and 121 healthy controls were enrolled． The BDKＲB2 + 9 /-9 polymorphisms were genotyped． The tumor necrosis factor ( TNF) -α，interleukin ( IL) -1β，IL-6 and IL-8 levels were determined using Enzyme-linked immunosorbent assay ( ELISA) ． The toll-like receptor ( TLＲ) -2 and TLＲ-4 mＲNA levels were determined by quantitative real-time PCＲ． The basal and bradykinin-stimulated pro-inflammatory cytokine secretion in human OA synoviocytes was investigated． Ｒesults In OA patients， significantly higher TNF-α and IL-8 levels were detected in the serum and synovial fluid of the BDKＲB2 -9 /-9 genotype carriers compared with the + 9 / + 9 carriers ( P ＜ 0. 05) ． IL-6 levels were significantly higher in the BDKＲB2 -9 /-9 and + 9 /-9 genotype carriers compared with the + 9 / + 9 ( P ＜ 0. 05) ． In the synovial tissue significantly higher TLＲ-2 mＲNA levels were detected in the + 9 /-9 and -9 /-9 carriers compared with the + 9 / + 9 carriers ( P ＜ 0. 01) ; TLＲ-2 silencing inhibited IL-6 and IL-8 secretion in human OA synoviocytes ( P ＜ 0. 01) ． Conclusion The data suggested that the BDKＲB2 + 9 /-9 polymorphisms influence proinflammatory cytokine levels in knee osteoarthritis by altering TLＲ-2 expression． [ABSTRACT FROM AUTHOR]