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| 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 |
| The BDKRB2 +9/-9 polymorphisms influence pro-inflammatory cytokine levels in knee osteoarthritis by altering TLR-2 expression |
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| DOI：10.3969/j.issn.1006-7108.2018.02.001 |
| 中文关键词: 缓激肽受体B2 基因多态性 骨关节炎 toll样受体-2 滑膜细胞 炎性细胞 骨质疏松 |
| 英文关键词:Bradykinin B2 receptor Gene polymorphism Osteoarthritis Toll-like receptor-2 Synoviocytes Inflammatory cells Osteoporosis |
| 基金项目:国家自然科学基金项目(81301582)；中国博士后科学基金面上项目(2015M572812) |
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| 中文摘要: |
| 目的 探究缓激肽B2受体（BDKRB2）+9/-9基因多态性和骨关节炎（osteoarthritis，OA）炎性细胞因子水平的关系，以及其涉及的分子机制。方法 共有156例膝关节OA患者及121名健康对照者被纳入研究。BDKRB2 +9/-9基因多态性被测定分型。用酶联免疫吸附试验(enzyme linked immunosorbent assay，ELISA)测定炎性细胞因子水平，包括肿瘤坏死因子（tumor necrosis factor，TNF）-α、白介素（interleukin，IL）-1β(IL-1β)、IL-6、IL-8。实时荧光定量（polymerase chain reaction，PCR）测定toll样受体（toll-like receptor，TLR）-2和TLR-4的mRNA水平。用ELISA测定TLR-2对基底和缓激肽（bradykinin，BK）刺激促进炎性细胞因子的分泌量。结果 在OA患者中-9/-9基因型组血清和滑液TNF-α和IL-8水平显著高于+9/+9组（P＜0.05）；而-9/-9和+9/-9基因型组IL-6水平显著高于+9/+9组。在滑膜组织中-9/-9和+9/-9基因型组的TLR-2 mRNA水平显著高于+9/+9基因型组（P＜0.01）。BDKRB2拮抗剂MEN16132和TLR-2沉默抑制IL-6和IL-8在人类OA滑膜细胞的分泌（P＜0.01）。结论 BDKRB2 +9/-9多态性可以通过改变TLR-2表达影响膝骨关节炎中的促炎性细胞因子水平。 |
| 英文摘要: |
| Objective To investigate the correlation between the bradykinin B2 receptor +9/-9 polymorphisms and pro-inflammatory 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 pro-inflammatory cytokine levels in knee osteoarthritis by altering TLR-2 expression. |
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