IL-17 regulates gene expression and protein synthesis of the complement system, C3 and factor B, in skin fibroblasts
IL-17 regulates gene expression and protein synthesis of the complement system, C3 and factor B, in skin fibroblasts
复制标题
DOI：
10.1046/j.1365-2249.2000.01199.x
复制
发表时间：
2000-04-01
影响因子：
4.6
通讯作者：
Loos, M
中科院分区：
文献类型：
--
作者：
Katz, Y;Nadiv, O;Loos, M
人IL-17是一种由CD 4（+）激活的记忆T细胞分泌的细胞因子，具有Th 1细胞因子的作用特征。IL-17对关节的许多细胞成分的作用表明它可能参与炎性关节疾病。已知补体系统的蛋白质受促炎和抗炎细胞因子调节。本研究的目的是研究IL-17单独和与肿瘤坏死因子（TNF）联合对因子B和C3表达和合成的影响。用相关的细胞因子刺激成纤维细胞，用S-35-甲硫氨酸脉冲标记，免疫沉淀新合成的蛋白质并进行SDS-PAGE。通过北方印迹分析测定基因表达。IL-17 10 ng/ml诱导C3基因表达和蛋白质合成分别增加2.25 +/- 0.26倍和2.7 +/- 0.7倍，同时对因子B的影响不显著，分别为1.5 +/- 0.45倍和2.2 +/- 1.2倍。当IL-17和TNF同时存在时，因子B的合成增加了85%，比这些细胞因子单独的预期加和效应多，而对于C3，两种细胞因子的效应比预期加和效应低19%（观察/预期= 0.81）。IL-4使协同效应降低50%。我们的结论是，IL-17具有调节作用的C3的表达和合成和放大效应的TNF诱导的因子B的合成。结合TNF是参与类风湿性关节炎炎症的主要细胞因子的证据，表明IL-17在关节的炎症过程中具有促炎作用。IL-4、IL-17和TNF对成纤维细胞中因子B合成的不同影响表明，因子B和补体系统的旁路途径可能在关节炎症中起重要作用。
Human IL-17 is a cytokine secreted by CD4(+)-activated memory T cells with the profile of effects of a Th1 cytokine. The effects of IL-17 on many cellular constituents of joints suggest that it may participate in inflammatory joint diseases. Proteins of the complement system are known to be regulated by pro- and anti-inflammatory cytokines. The purpose of this work was to study the effect of IL-17 alone and combined with tumour necrosis factor (TNF) on the expression and synthesis of factor B and C3. Fibroblasts were stimulated with the relevant cytokine or cytokines, pulse labelled with S-35-methionine, and the newly synthesized proteins were immunoprecipitated and subjected to SDS-PAGE. Gene expression was determined by Northern blot analysis. IL-17 10 ng/ml induced increases in gene expression and protein synthesis of C3, 2.25 +/- 0.26- and 2.7 +/- 0.7-fold, respectively, with concomitant non-significant effects on factor B, 1.5 +/- 0.45- and 2.2 +/- 1.2-fold, respectively. When both IL-17 and TNF were present simultaneously, the synthesis of factor B increased by 85% more than the expected additive effects of these cytokines separately, while for C3 the effect of both cytokines was 19% lower than the expected additive effect (observed/expected = 0.81). IL-4 reduced the synergistic effect by 50%. We conclude that IL-17 has a regulatory role on C3 expression and synthesis and an amplifying effect on TNF-induced factor B synthesis. Taken together with the evidence that TNF is a major cytokine involved in the inflammation of rheumatoid arthritis, it suggests that IL-17 has a proinflammatory role in the inflammation process of joints. The distinct effects of IL-4, IL-17 and TNF on the synthesis of factor B in fibroblasts suggest that factor B and the alternative pathway of the complement system may play an important role in joint inflammation.