The anti-inflammatory actions of IL-4 in human monocytes are not mediated by IL-10, RP105 or the kinase activity of RIPK2
- Author(s)
- Woodward, EA; Kolesnik, TB; Nicholson, SE; Prele, CM; Hart, PH;
- Details
- Publication Year 2012-06,Volume 58,Issue #3,Page 415-423
- Journal Title
- CYTOKINE
- Publication Type
- Journal Article
- 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 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 alpha 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 TNF alpha 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. (C) 2012 Elsevier Ltd. All rights reserved.
- Publisher
- ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
- Keywords
- Monocytes/macrophages ; Toll-like receptor signaling ; Interleukin-4 ; Interleukin-10 ; RP105
- Research Division(s)
- Inflammation
- Publisher's Version
- https://doi.org/10.1016/j.cyto.2012.03.009
- Terms of Use/Rights Notice
- Copyright © 2012 Elsevier Ltd. All rights reserved.
Creation Date: 2012-06-01 12:00:00