Mechanism of inhibition of LPS-induced IL-12p40 production by IL-10 and TGF-β in ANA-1 cells
Mechanism of inhibition of LPS-induced IL-12p40 production by IL-10 and TGF-β in ANA-1 cells
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DOI：
10.1002/jlb.64.1.92
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发表时间：
1998-07-01
影响因子：
5.5
通讯作者：
Sriram, S
中科院分区：
文献类型：
--
作者：
Du, CG;Sriram, S
IL-12是一种巨噬细胞来源的促炎细胞因子，由两个不同的基因编码的两个多肽亚基(p40和p35)组成。P35亚基是结构性表达的，而p40亚基是在激活后诱导的，生物活性白介素12(IL-12；p70)影响Th1反应的发展，是自然杀伤(NK)和T细胞的强大激活剂。与IL-12相反，转化生长因子β(TGF-β)和IL-10抑制包括IL-12在内的促炎细胞因子的产生，并减弱Th1介导的免疫反应。我们研究了转化生长因子-β和IL-10抑制脂多糖刺激的小鼠巨噬细胞产生IL-12p40亚单位的分子机制，结果表明，IL-10和转化生长因子-β均通过抑制IL-12p40基因的转录而抑制IL-12p40的产生。在相同浓度下，IL-10对IL-12p40基因转录的抑制作用强于转化生长因子-β。转化生长因子-β也降低了IL-12p40mRNA的稳定性，从而解释了另一种抑制IL-12产生的机制。
IL-12, a macrophage-derived proinflammatory cytokine, consists of two polypeptide subunits (p40 and p35) encoded by two separate genes. The p35 subunit is constitutively expressed, whereas the p40 subunit is induced after activation, The bioactive interleukin-12 (IL-12; p70) influences the development of Th1 responses and is a potent activator of natural killer (NK) and T cells. In contrast to IL-12, transforming growth factor beta (TGF-beta) and IL-10 inhibit production of proinflammatory cytokines, including IL-12, and attenuate Th1-mediated immune response. We have examined the molecular mechanisms by which TGF-beta and IL-10 inhibit production of the IL-12p40 subunit in LPS-stimulated murine macrophage cell line, We show that both IL-10 and TGF-beta suppress IL-12p40 production by inhibiting the transcription of IL-12p40 gene. At equal concentrations, IL-10 was more potent than TGF-beta in inhibiting IL-12p40 gene transcription. TGF-beta also reduces the stability of IL-12p40 mRNA, accounting thereby to an additional mechanism of inhibition of IL-12 production.