Direct contact between T lymphocytes and human dermal fibroblasts or synoviocytes down-regulates types I and III collagen production via cell-associated cytokines
Direct contact between T lymphocytes and human dermal fibroblasts or synoviocytes down-regulates types I and III collagen production via cell-associated cytokines
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DOI：
10.1074/jbc.273.30.18720
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发表时间：
1998-07-24
影响因子：
4.8
通讯作者：
Dayer, JM
中科院分区：
文献类型：
--
作者：
Rezzonico, R;Burger, D;Dayer, JM
在许多发生组织重塑的炎性疾病中，T细胞与间充质细胞密切接触。我们研究了外周血T淋巴细胞或HUT-78淋巴瘤细胞与真皮成纤维细胞或滑膜细胞之间的直接细胞-细胞接触对主要细胞外基质成分（I型和III型胶原）沉积的影响。孵育真皮成纤维细胞和滑膜细胞质膜制剂从休息T细胞略有增加生产的胶原蛋白I，但没有显着影响的胶原蛋白III。相反，直接接触质膜或固定的植物血凝素/佛波醇肉豆蔻酸酯激活的T细胞显着抑制60-70%，在未经处理的皮肤成纤维细胞和滑膜细胞和85%，在转化生长因子β刺激的成纤维细胞的I型和III型胶原蛋白的合成。当固定的T细胞与成纤维细胞物理分离时，胶原合成的减少被消除，表明两种细胞类型之间的直接接触是必要的。这种抑制与前-α 1（I）和前-α 1（III）胶原mRNA的稳态水平显著降低相关。T细胞接触降低了转录速率，但没有显着改变α 1（I）和α 1（III）转录的稳定性。最后，使用中和抗体或细胞因子抑制剂，我们提供的证据表明，T细胞接触介导的细胞外基质产生的这种抑制部分是由于T细胞膜相关的干扰素γ，肿瘤坏死因子α和白细胞介素-1 α的累加效应。
In many inflammatory diseases where tissue remodeling occurs, T cells are in close contact with mesenchymal cells. We investigated the effect of direct cell-cell contact between peripheral blood T lymphocytes or HUT-78 lymphoma cells and dermal fibroblasts or synoviocytes on the deposition of the major extracellular matrix components: types I and III collagen. Incubation of dermal fibroblasts and synoviocytes with plasma membrane preparations from resting T cells slightly increased the production of collagen I but did not significantly affect that of collagen III. Conversely, direct contact with either plasma membranes or fixed phytohemagglutinin/phorbol myristate acetate activated T cells markedly inhibited the synthesis of types I and III collagen by 60-70% in untreated dermal fibroblasts and synoviocytes and by 85% in transforming growth factor beta-stimulated fibroblasts. This decrease of collagen synthesis was abrogated when fixed T cells were separated physically hom fibroblasts, demonstrating that direct contact between the two cell types was necessary. This inhibition was associated with a marked decrease in steady-state levels of pro-alpha 1(I) and pro-alpha 1(III) collagen mRNAs. T cell contact decreased the transcription rate but did not significantly alter the stability of the alpha 1(I) and alpha 1(III) transcripts. Finally, using neutralizing antibodies or cytokine inhibitors we provide evidence that this inhibition of extracellular matrix production mediated by T cell contact was partially due to additive effects of T cell membrane-associated interferon gamma, tumor necrosis factor alpha, and interleukin-1 alpha.