The anti-inflammatory actions of IL-4 in human monocytes are not mediated by IL-10, RP105 or the kinase activity of RIPK2

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• 作者：Eleanor A. Woodward^a ; ^b ; Tatiana B. Kolesnik^c ; Sandra E. Nicholson^c ; Cecilia M. Prê ; le^a ; ¹ ; Prue H. Hart^a ; ^{prueh@ichr.uwa.edu.au}
• 关键词：BMM ; bone marrow-derived macrophages ; GM-CSF ; granulocyte macrophage-colony stimulating factor ; IRS ; insulin receptor substrate ; MFI ; mean fluorescence intensity ; MAPK ; mitogen-activated protein kinase ; M-CSF ; macrophage-colony stimulating factor ; PBMC ; p
• 刊名：Cytokine
• 出版年：2012
• 期刊代码：97_10434666
• 类别：imm
• 出版时间：June, 2012
• 卷：58
• 期：3
• 页码：415-423
• 文件大小：930 K

摘要

The anti-inflammatory actions of IL-4 in activated human monocytes may reflect transcriptional regulation of genes involved in TLR signaling pathways. Tailored gene arrays were conducted to profile the expression of 84 genes central to TLR-mediated signal transduction in human monocytes treated with the TLR4 ligand, LPS, with or without IL-4. In the first 3 h, IL-4 down-regulated mRNA levels of LPS-induced inflammatory cytokines and chemokines, without altering mRNA levels of TLRs, TLR-related signaling molecules or multiple transcription factors. The down-regulation of inflammatory genes by IL-4 was preceded by an early up-regulation of IL-10 mRNA and protein and mRNA for receptor-interacting serine-threonine kinase 2 (RIPK2), the TLR homolog, RP105, and c-Maf, a transcription factor required for IL-10 gene expression. However, IL-4 still suppressed LPS-induced TNF伪 production in bone-marrow derived macrophages from IL10^{鈭?鈭?/sup> mice, and in the presence of a neutralizing antibody to IL-10 in human monocytes. The up-regulation of RIPK2 and RP105 mRNA by IL-4 occurred independently of IL-10. IL-4 maintained the ability to suppress LPS-induced TNF伪 and enhance IL-10 production in the presence of RIPK2 kinase inhibitors. Further, IL-4 failed to up-regulate expression of RP105 at the cell surface. In conclusion, the anti-inflammatory actions of IL-4 occur independently of IL-10, RP105, and the kinase activity of RIPK2.}