INFLUENCES OF GAMMA-INTERFERON ON SYNOVIAL FIBROBLAST-LIKE CELLS - IA INDUCTION AND INHIBITION OF COLLAGEN-SYNTHESIS
INFLUENCES OF GAMMA-INTERFERON ON SYNOVIAL FIBROBLAST-LIKE CELLS - IA INDUCTION AND INHIBITION OF COLLAGEN-SYNTHESIS
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DOI：
10.1172/jci112041
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发表时间：
1985-01-01
影响因子：
15.9
通讯作者：
KRANE, SM
中科院分区：
文献类型：
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作者：
AMENTO, EP;BHAN, AK;KRANE, SM
从人类风湿关节滑膜培养的粘附细胞的形状和功能受到免疫细胞及其产物的影响。滑膜细胞产生胶原酶和前列腺素E2（PGE 2），当细胞与单核细胞因子/白细胞介素1孵育时，其水平增加。大多数粘附的滑膜细胞在外观上是成纤维细胞样的，并合成胶原和纤连蛋白;胶原和纤连蛋白的合成也通过单核细胞因子增加。成纤维细胞样细胞表达主要组织相容性复合物II类（IA样）抗原后，从滑膜初始分散。单核细胞系抗原检测到一些圆形细胞在早期传代，但没有T淋巴细胞被确定在建立的文化。随着年龄的增长和传代培养，成纤维细胞样细胞上Ia表达丧失。淋巴因子γ的添加干扰素（重组）以时间和剂量依赖性方式诱导早期或晚期传代细胞中的II类抗原（DR和DS/DQ）表达，并需要蛋白质合成。当在去除γ后长达10天进行检查时，粘附的滑膜成纤维细胞样细胞继续为Ia阳性。干扰素γ也诱导了Ia表达。正常皮肤成纤维细胞中的干扰素。可以被诱导表达Ia的滑膜细胞也结合了III型胶原（成纤维细胞标记物）的单克隆抗体。γ。干扰素，而诱导Ia的表达，降低了III型胶原抗体的结合，以及单核细胞因子刺激的细胞上的未刺激的。通过SDS [十二烷基硫酸钠]聚丙烯酰胺凝胶电泳分析[3 H]脯氨酸标记的培养基显示γ干扰素以剂量依赖性方式减少粘附滑膜细胞合成I型和III型胶原和纤连蛋白。滑膜组织细胞的Ia表达不是细胞特异性的，而是反映了一种或几种相关事件，如T淋巴细胞浸润的程度、刺激γ的因子的存在、以及免疫反应的程度。干扰素释放，或细胞对γ的敏感性增加。干扰素而II类抗原的合成被淋巴因子γ增强。干扰素和单核细胞因子刺激相同细胞的胶原蛋白、胶原酶和PGE 2合成，干扰素抑制基础和单核因子诱导的胶原合成。与类风湿病变不同阶段的基质破坏相比，类风湿因子和单核因子可能通过影响成纤维细胞样滑膜细胞的功能来影响纤维化的程度。
The shape and function of adherent cells cultured from human rheumatoid synovial membranes are influenced by immune cells, and their products. The synovial cells produce collagenase and prostaglandin E2 (PGE2), the levels of which are increased when the cells are incubated with the monokine, mononuclear cell factor/interleukin 1. The majority of adherent synovial cells are fibroblastlike in appearance and synthesize collagens and fibronectin; the synthesis of collagens and fibronectins are also increased by a monocyte factor. The fibroblastlike cells expressed major histocompatibility complex class II (Ia-like) antigens after initial dispersion from the synovial membrane. Monocyte lineage antigens were detected on some round cells in early passage, but no T lymphocytes were identified in established cultures. There was loss of Ia expression on the fibroblastlike cells with age and passage in culture. The addition of the lymphokine, .gamma. interferon (recombinant), induced class II antigen (DR and DS/DQ) expression in early or late passage cells in a time- and dose-dependent manner and required protein synthesis. The adherent synovial fibroblastlike cells continued to be Ia-positive when examined as long as 10 day after the removal of .gamma. interferon. Ia expression was also induced by .gamma. interferon in normal skin fibroblasts. Synovial cells that could be induced to express Ia also bound a monoclonal antibody to type III collagen (a fibroblast marker). .gamma. Interferon, while inducing Ia expression, decreased the binding of type III collagen antibody on unstimulated as well as monokine-stimulated cells. Analysis of [3H]proline-labeled medium by SDS [sodium dodecyl sulfate] polyacrylamide gel electrophoresis showed that .gamma. interferon decreased the synthesis of type I and III collagens and fibronectin by adherent synovial cells in a dose-dependent manner. Ia expression by synovial tissue cells is not cell-specific, but reflects 1 or several related events, such as the degree of T lymphocyte infiltration, the presence of factors that stimulate .gamma. interferon release, or an increased sensitivity of the cells to .gamma. interferon. Whereas the synthesis of class II antigens is enhanced by the lymphokine .gamma. interferon, and a monocyte factor(s) stimulates collagen, collagenase and PGE2 synthesis by the same cells, .gamma. interferon inhibits basal and monokine-induced collagen synthesis. Lymphokines and monokines may influence the extent of fibrosis as contrasted to matrix destruction at various stages of the rheumatoid lesion by affecting the function of fibroblastlike synovial cells.