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

Woodward, E.A., Kolesnik, T.B., Nicholson, S.E., Prêle, C.M. and Hart, P.H. (2012) The anti-inflammatory actions of IL-4 in human monocytes are not mediated by IL-10, RP105 or the kinase activity of RIPK2. Cytokine, 58 (3). pp. 415-423.

Link to Published Version: http://dx.doi.org/10.1016/j.cyto.2012.03.009
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Abstract

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 3h, 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 TNFα production in bone-marrow derived macrophages from IL10 -/- 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 TNFα 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.

Publication Type: Journal Article
Publisher: Academic Press Inc.
Copyright: © 2012 Elsevier Ltd.
URI: http://researchrepository.murdoch.edu.au/id/eprint/8544
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