Interleukin-10 (IL-10) selectively enhances CIS3/SOCS3 mRNA expression in human neutrophils: Evidence for an IL-10-induced pathway that is independent of STAT protein activation
Interleukin-10 (IL-10) selectively enhances CIS3/SOCS3 mRNA expression in human neutrophils: Evidence for an IL-10-induced pathway that is independent of STAT protein activation
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DOI：
10.1182/blood.v94.8.2880.420k31_2880_2889
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发表时间：
1999-10-15
期刊：
影响因子：
20.3
通讯作者：
Yoshimura, A
中科院分区：
文献类型：
--
作者：
Cassatella, MA;Gasperini, S;Yoshimura, A
我们最近发现，在人的中性粒细胞中，白细胞介素10(IL-10)不能诱导与γ-干扰素反应区(GRR)的特异性DNA结合活性，GRR是位于Fc-γRI基因启动子的一个调节元件，是IL-10和单核细胞中的干扰素-γ(干扰素-γ)转录激活所必需的。在这项研究中，我们报告了IL-10也不能诱导STAT1或STAT3与血清诱导元件(HSIE/M67)的结合，尽管这两种蛋白都在中性粒细胞中表达。干扰素和粒细胞集落刺激因子(G-CSF)是中性粒细胞(PMN)STAT1和STAT3酪氨酸磷酸化的有效诱导剂，而IL-10不能激活STAT1和STAT3酪氨酸和丝氨酸磷酸化，从而解释了其不能诱导这些细胞FcγRI表达的原因。相反，我们证明了IL-10单独代表了中性粒细胞中CIS3/SOCS3基因表达的有效刺激。Cis3/SOCS3属于最近克隆的细胞因子诱导的SH2蛋白(CIS)基因家族(还包括Cis1、Cis2、Cis4、Cis5和Jab)，被认为至少部分受STAT转录因子的控制，其产物是潜在的细胞因子信号调节因子。此外，IL-10与脂多糖(LPS)通过一种涉及mRNA稳定的机制协同上调PMN中CIS3/SOCS3的mRNA表达。与C1S3/SOCS3不同，中性粒细胞中编码其他家族成员的mRNA转录本不受IL-10的影响。最后，在小鼠M1髓系细胞中转导CIS3/SOCS3可抑制脂多糖诱导的生长停滞、巨噬细胞样分化和一氧化氮合成，但不能抑制IL-6mRNA的表达。总之，我们的数据表明，在中性粒细胞中，激活STAT1和STAT3磷酸化既不是IL-10诱导CIS3/SOCS3所必需的，也不参与IL-10对细胞因子产生的调节作用。(C)1999年由美国血液病学会主办。
We have recently shown that, in human neutrophils, interleukin-10 (IL-10) fails to induce specific DNA-binding activities to the gamma-interferon response region (GRR), a regulatory element located in the Fc gamma RI gene promoter, which is required for transcriptional activation by IL-10 and interferon gamma (IFN gamma) in monocytic cells. In this study, we report that IL-10 is also unable to induce the binding of STAT1 or STAT3 to the serum-inducible element (hSIE/m67), despite the fact that both proteins are expressed in neutrophils. Whereas IFN gamma and granulocyte colony-stimulating factor (G-CSF) are efficient inducers of STAT1 and STAT3 tyrosine phosphorylation in polymorphonuclear neutrophils (PMN), IL-10 fails to trigger STAT1 and STAT3 tyrosine and serine phosphorylation, therefore explaining its inability to induce the Fc gamma RI expression in these cells. By contrast, we demonstrate that IL-10 alone represents an efficient stimulus of CIS3/SOCS3 mRNA expression in neutrophils. CIS3/SOCS3 belongs to the recently cloned cytokine-inducible SH2-containing protein (CIS) gene family (which also includes CIS1, CIS2, CIS4, CIS5, and JAB) that is believed to be, at least in part, under the control of STAT transcription factors and whose products are potential modulators of cytokine signaling. Moreover, IL-10 synergizes with lipopolysaccharide (LPS) in upregulating CIS3/SOCS3 mRNA expression in PMN through a mechanism that involves mRNA stabilization. in contrast to C1S3/SOCS3, mRNA transcripts encoding other family members are unaffected by IL-10 in neutrophils. Finally, transfection of CIS3/SOCS3 in murine M1 myeloid cells suppresses LPS-induced growth arrest, macrophage-like differentiation, and nitric oxide synthesis, but not IL-6 mRNA expression. Collectively, our data suggest that, in neutrophils, the activation of STAT1 and STAT3 phosphorylation is neither required for CIS3/SOCS3 induction by IL-10 nor involved in the regulatory effects of IL-10 on cytokine production. (C) 1999 by The American Society of Hematology.