CYTOKINE-INDUCED EXPRESSION OF MESSENGER-RNAS FOR CHEMOTACTIC FACTORS IN HUMAN SYNOVIAL-CELLS AND FIBROBLASTS

CYTOKINE-INDUCED EXPRESSION OF MESSENGER-RNAS FOR CHEMOTACTIC FACTORS IN HUMAN SYNOVIAL-CELLS AND FIBROBLASTS
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DOI:
10.1002/jcp.1041540227
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发表时间:
1993-02-01
影响因子:
5.6
通讯作者:
GOLDS, EE
GOLDS, EE
中科院分区:
生物学2区
文献类型:
--
作者:
BEDARD, PA;GOLDS, EE

文献摘要

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为了响应白细胞介素 1 或肿瘤坏死因子,人类滑膜细胞和成纤维细胞表达多种编码已知趋化因子或相关蛋白的基因。白介素 8 (IL-8)、gro/MGSA、pAT 464、IP-10、pAT 744 和单核细胞趋化和激活因子 (MCAF) 的转录物在 IL-1 和 TNF 处理的细胞中快速积累。蛋白质合成的抑制导致 IL-1 中 IL-8 和 gro/MGSA mRNA 的超诱导,但在 TNF 处理的细胞中则不然。因此,IL-1和TNF可能通过不同的机制调节这些mRNA的表达。 mRNA 积累的重要细胞特异性差异表征了趋化因子基因的表达。此外,在血清刺激的静止细胞中,只有一部分相同基因被激活。因此,编码密切相关蛋白质的基因各自具有不同的表达模式。用 IL-1 持续刺激成纤维细胞和滑膜细胞导致 IL-8 和 gro/MGSA mRNA 的高表达和延长表达。这些结果扩展了间充质细胞在体外表达的趋化因子基因的列表,并表明这些细胞在慢性炎症等过程中发挥着关键作用。
In response to interleukin 1 or tumor necrosis factor, human synovial cells and fibroblasts expressed several genes encoding known chemotactic factors or related proteins. Transcripts for interleukin 8 (IL-8), gro/MGSA, pAT 464, IP-10, pAT 744 and Monocyte Chemotactic and Activating Factor (MCAF) accumulated rapidly in IL-1 and TNF-treated cells. The inhibition of protein synthesis led to the superinduction of IL-8 and gro/MGSA mRNAs in IL-1, but not in TNF-treated cells. Thus, IL-1 and TNF are likely to regulate the expression of these mRNAs by different mechanisms. Important cell-specific differences in mRNA accumulation characterized the expression of chemotactic factor genes. Moreover, only a subset of the same genes was activated in quiescent cells stimulated by serum. Therefore, genes encoding closely related proteins each had a distinct pattern of expression. Continuous stimulation of fibroblasts and synovial cells with IL-1 resulted in high and prolonged expression of IL-8 and gro/MGSA mRNAs. These results extend the list of chemotactic factor genes expressed by mesenchymal cells in vitro and suggest a pivotal role for these cells in processes such as chronic inflammation.