Journal article
The anti-inflammatory actions of IL-4 in human monocytes are not mediated by IL-10, RP105 or the kinase activity of RIPK2
Cytokine, Vol.58(3), pp.415-423
2012
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.
Details
- Title
- The anti-inflammatory actions of IL-4 in human monocytes are not mediated by IL-10, RP105 or the kinase activity of RIPK2
- Authors/Creators
- E.A. Woodward (Author/Creator) - The Kids Research Institute AustraliaT.B. Kolesnik (Author/Creator) - Walter and Eliza Hall Institute of Medical ResearchS.E. Nicholson (Author/Creator) - Walter and Eliza Hall Institute of Medical ResearchC.M. Prêle (Author/Creator) - The Kids Research Institute AustraliaP.H. Hart (Author/Creator) - The Kids Research Institute Australia
- Publication Details
- Cytokine, Vol.58(3), pp.415-423
- Publisher
- Academic Press Inc.
- Identifiers
- 991005544626007891
- Copyright
- © 2012 Elsevier Ltd.
- Murdoch Affiliation
- Murdoch University
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.6 Immunology
- 1.6.609 Toll-like Receptors
- Web Of Science research areas
- Biochemistry & Molecular Biology
- Cell Biology
- Immunology
- ESI research areas
- Molecular Biology & Genetics