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细胞因子对正常及转化滑膜细胞MHC抗原和细胞间黏附分子-1表达的影响。

The effect of cytokines on the expression of MHC antigens and ICAM-1 by normal and transformed synoviocytes.

作者信息

Wicks I P, Leizer T, Wawryk S O, Novotny J R, Hamilton J, Vitti G, Boyd A W

机构信息

Lions Laboratory, Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Australia.

出版信息

Autoimmunity. 1992;12(1):13-9. doi: 10.3109/08916939209146125.

Abstract

We report the expression on synovial cells of cell surface molecules known to be involved in T cell activation by antigen presenting cells. Normal human synovial fibroblasts and a human synovial cell line transformed with the SV40 large T antigen were used for in vitro stimulation studies with recombinant cytokines. We demonstrate an increase in MHC-A, B, C expression in normal synovial cells in response to recombinant interferon gamma (r gamma IFN), tumour necrosis factor alpha and beta (rTNF alpha and beta) and interleukin-1 (rIL-1 alpha). Intercellular adhesion molecular-1 (ICAM-1) expression was increased in parallel with MHC Class I. The combination of r gamma IFN and rTNF alpha was additive in its effect on ICAM-1 expression. Northern blot analysis suggests that ICAM-1 expression in synovial cells is controlled at the level of transcription. In contrast, MHC Class II (HLA-DR) was only significantly induced by r gamma IFN. Other stimuli including interleukin-4 (IL-4), interleukin 6 (IL-6), granulocyte macrophage colony stimulating factor (GM-CSF) and prostaglandin E2 (PGE2) did not affect the expression of ICAM-1 or MHC Class I and II. Leucocyte function antigen 3 (LFA-3) expression was not affected by any of the stimuli tested. Immunoperoxidase staining of rheumatoid synovial tissue confirmed enhanced in vivo expression of ICAM-1 in rheumatoid arthritis. These changes are discussed in the context of T cell activation in inflammatory arthritis.

摘要

我们报道了已知参与抗原呈递细胞激活T细胞的细胞表面分子在滑膜细胞上的表达情况。使用正常人滑膜成纤维细胞和用SV40大T抗原转化的人滑膜细胞系进行重组细胞因子的体外刺激研究。我们证明,在重组干扰素γ(rγIFN)、肿瘤坏死因子α和β(rTNFα和β)以及白细胞介素-1(rIL-1α)作用下,正常滑膜细胞中MHC-A、B、C的表达增加。细胞间黏附分子-1(ICAM-1)的表达与MHC I类分子的表达平行增加。rγIFN和rTNFα联合使用对ICAM-1表达具有相加作用。Northern印迹分析表明,滑膜细胞中ICAM-1的表达在转录水平受到调控。相比之下,MHC II类分子(HLA-DR)仅在rγIFN作用下显著诱导表达。包括白细胞介素-4(IL-4)、白细胞介素-6(IL-6)、粒细胞巨噬细胞集落刺激因子(GM-CSF)和前列腺素E2(PGE2)在内的其他刺激因素均不影响ICAM-1或MHC I类和II类分子的表达。白细胞功能抗原3(LFA-3)的表达不受任何测试刺激因素的影响。类风湿性滑膜组织的免疫过氧化物酶染色证实,类风湿性关节炎中ICAM-1在体内的表达增强。在炎症性关节炎中T细胞激活的背景下对这些变化进行了讨论。

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