Increased expression of pro-inflammatory cytokines and metalloproteinase-1 by TGF-β1 in synovial fibroblasts from rheumatoid arthritis and normal individuals
Increased expression of pro-inflammatory cytokines and metalloproteinase-1 by TGF-β1 in synovial fibroblasts from rheumatoid arthritis and normal individuals
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DOI：
10.1046/j.1365-2249.2002.01785.x
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发表时间：
2002-03-01
影响因子：
4.6
通讯作者：
Sohn, J
中科院分区：
文献类型：
--
作者：
Cheon, H;Yu, SJ;Sohn, J
转化生长因子-β1在类风湿滑膜中大量表达。本研究利用培养的类风湿关节炎(RA)和骨关节炎(OA)患者及非关节炎患者的成纤维细胞样滑膜细胞(FLS)，研究了转化生长因子-β1在类风湿关节炎(RA)中的炎症作用。IL-1β、肿瘤坏死因子(TNF)-α、IL-8、巨噬细胞炎性蛋白(MIP)-1α和金属蛋白酶(MMP)-1在RA和OA FLS中的表达增加，而在非关节炎FLS中的表达无明显变化。RA FLS中IL-1β、IL-8和MMP-1的蛋白表达也明显增强。此外，转化生长因子-β1分别与肿瘤坏死因子α和IL-1β协同促进IL-1β和基质金属蛋白酶-1的蛋白表达。经小鼠胸腺细胞增殖实验检测，RA FLS培养上清液中的转化生长因子-β1可使IL-1的生物活性增加50%。转化生长因子-β1对核因子-kappaB和激活蛋白-1的DNA结合活性也有增强作用。这些结果表明，转化生长因子-β1参与了类风湿性关节炎炎症和关节破坏的进展，并且这种作用是关节炎滑膜成纤维细胞所特有的。
Transforming growth factor (TGF)-beta1 is expressed abundantly in the rheumatoid synovium. In this study, the inflammatory effect of TGF-beta1 in rheumatoid arthritis (RA) was investigated using cultured fibroblast-like synoviocytes (FLS) from RA and osteoarthritis (OA) patients, as well as non-arthritic individuals. mRNA expressions of IL-1beta, tumour necrosis factor (TNF)-alpha, IL-8, macrophage inflammatory protein (MIP)-1alpha and metalloproteinase (MMP)-1 were increased in RA and OA FLS by TGF-beta1 treatment, but not in non-arthritic FLS. Enhanced protein expression of IL-1beta, IL-8 and MMP-1 was also observed in RA FLS. Moreover, TGF-beta1 showed a synergistic effect in increasing protein expression of IL-1beta and matrix metalloproteinase (MMP)-1 with TNFalpha and IL-1beta, respectively. Biological activity of IL-1 determined by mouse thymocyte proliferation assay was also enhanced by 50% in response to TGF-beta1 in the culture supernatant of RA FLS. DNA binding activities of nuclear factor (NF)-kappaB and activator protein (AP)-1 were shown to increase by TGF-beta1 as well. These results suggest that TGF-beta1 contributes for the progression of inflammation and joint destruction in RA, and this effect is specific for the arthritic synovial fibroblasts.