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白细胞介素-6在外周血单个核细胞和U937细胞系中诱导单核细胞趋化蛋白-1的产生。

Interleukin-6 induces monocyte chemotactic protein-1 in peripheral blood mononuclear cells and in the U937 cell line.

作者信息

Biswas P, Delfanti F, Bernasconi S, Mengozzi M, Cota M, Polentarutti N, Mantovani A, Lazzarin A, Sozzani S, Poli G

机构信息

AIDS Immunopathogenesis Unit, DIBIT, and the Division of Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy.

出版信息

Blood. 1998 Jan 1;91(1):258-65.

PMID:9414293
Abstract

Induction of chemokine gene expression from peripheral blood mononuclear cells (PBMCs) stimulated by proinflammatory cytokines plays an important role in both wound repair and response to infectious agents. In the present study, we show that the proinflammatory cytokine interleukin-6 (IL-6) potently induced mRNA expression and secretion of the CC chemokine monocyte chemotactic protein 1 (MCP-1) in PBMCs. In addition, because human immunodeficiency virus (HIV) infection in vivo and in vitro has been shown to dysregulate the production of and/or the response to cytokines, PBMCs from both healthy uninfected and HIV-infected individuals were studied for their constitutive and IL-6-induced expression of MCP-1. No substantial differences were observed between the two groups of individuals. In addition, IL-6 upregulated MCP-1 expression in the promonocytic cell line U937 and in its chronically HIV-infected counterpart, U1. In these cell lines, IL-6 selectively induced MCP-1 and not other chemokines, including regulated upon activation normal T cells expressed and secreted (RANTES), macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-1beta, and IL-8. IL-6 induction of MCP-1 was partially inhibited by hydrocortisone in U1 cells. Thus, IL-6 activates PBMCs to secrete MCP-1, a CC chemokine pivotal for monocyte recruitment in tissue and organs in which important inflammatory events occur.

摘要

促炎细胞因子刺激外周血单核细胞(PBMC)诱导趋化因子基因表达在伤口修复和对感染因子的反应中均发挥重要作用。在本研究中,我们发现促炎细胞因子白细胞介素-6(IL-6)能有效诱导PBMC中CC趋化因子单核细胞趋化蛋白1(MCP-1)的mRNA表达及分泌。此外,由于体内外人类免疫缺陷病毒(HIV)感染已显示会失调细胞因子的产生和/或对细胞因子的反应,因此我们研究了健康未感染个体和HIV感染个体的PBMC中MCP-1的组成性表达及IL-6诱导的表达情况。两组个体之间未观察到实质性差异。此外,IL-6上调了单核细胞系U937及其慢性HIV感染对应物U1中MCP-1的表达。在这些细胞系中,IL-6选择性诱导MCP-1,而非其他趋化因子,包括活化正常T细胞表达和分泌的调节因子(RANTES)、巨噬细胞炎性蛋白-1α(MIP-1α)、MIP-1β和IL-8。在U1细胞中,氢化可的松部分抑制了IL-6对MCP-1的诱导。因此,IL-6激活PBMC分泌MCP-1,MCP-1是一种CC趋化因子,对在发生重要炎症事件的组织和器官中单核细胞的募集至关重要。

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