CXCL16 upregulates RANKL expression in rheumatoid arthritis synovial fibroblasts through the JAK2/STAT3 and p38/MAPK signaling pathway
CXCL16 upregulates RANKL expression in rheumatoid arthritis synovial fibroblasts through the JAK2/STAT3 and p38/MAPK signaling pathway
复制标题
CXCL16通过JAK2/STAT3和p38/MAPK信号通路上调类风湿性关节炎滑膜成纤维细胞中RANKL的表达
DOI：
10.1007/s00011-015-0905-y
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发表时间：
2016-03-01
影响因子：
6.7
通讯作者：
Liu, Xiang-yuan
中科院分区：
文献类型：
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作者：
Li, Chang-hong;Xu, Lin-lin;Liu, Xiang-yuan
目的探讨趋化因子CXCL 16对类风湿关节炎（RA）成纤维样滑膜细胞（RA FLS）中受体活化因子核因子κ B配体（RANKL）表达的影响。采用酶联免疫吸附法（ELISA）测定血清CXCL 16和RANKL浓度。结果RA患者滑膜组织中CXCL 16、CXCR 6和RANKL的表达均高于OA患者，RA患者滑膜组织中RANKL的表达高于OA患者。RA患者血清CXCL 16和RANKL水平高于OA患者和健康对照组。CXCL 16与血沉、C反应蛋白、疾病活动度、血清类风湿因子和RANKL相关。用CXCL 16处理的RA-FLS显示RANKL表达显著增加。当STAT 3或p38激活被抑制剂阻断时，CXCL 16不能上调RANKL表达。结论CXCL 16可上调RA-FLS中RANKL的表达，其作用主要通过JAK 2/STAT 3和p38/MAPK信号通路介导。
Objective To explore the influence of chemokine, CXCL16, on the expression of the receptor activator nuclear factor kappa B ligand (RANKL) in rheumatoid arthritis (RA) fibroblast-like synoviocytes (RA-FLS).Methods The expression of CXCL16/CXCR6 and RANKL in RA or osteoarthritis (OA) patient synovia was examined by Western blot and immunohistochemistry. The serum concentration of CXCL16 and RANKL was measured by enzyme-linked immunosorbent assay (ELISA). RA-FLS were treated with recombinant CXCL16, and RANKL mRNA and protein were measured using PCR, Western blot and ELISA.Results The synovial expression of CXCL16, CXCR6, and RANKL was higher in RA patients than in patients with OA. The serum CXCL16 and RANKL levels were higher in RA patients compared with OA patients and healthy controls. CXCL16 correlated with erythrocyte sedimentation rate, C reactive protein, disease activity, serum rheumatoid factor, and RANKL. RA-FLS treated with CXCL16 showed markedly increased expression of RANKL. When STAT3 or p38 activation was blocked by an inhibitor, CXCL16 failed to upregulate RANKL expression. In contrast, inhibiting the Akt or Erk pathway did not achieve the same effect.Conclusions CXCL16 upregulates RANKL expression in RA-FLS and these effects are mainly mediated by the JAK2/STAT3 and p38/MAPK signaling pathways.