PMID- 22484241 OWN - NLM STAT- MEDLINE DCOM- 20120827 LR - 20120430 IS - 1096-0023 (Electronic) IS - 1043-4666 (Linking) VI - 58 IP - 3 DP - 2012 Jun TI - The anti-inflammatory actions of IL-4 in human monocytes are not mediated by IL-10, RP105 or the kinase activity of RIPK2. PG - 415-23 LID - 10.1016/j.cyto.2012.03.009 [doi] AB - 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 TNFalpha 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 TNFalpha 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. CI - Copyright (c) 2012 Elsevier Ltd. All rights reserved. FAU - Woodward, Eleanor A AU - Woodward EA AD - Inflammation Laboratory, Telethon Institute for Child Health Research and Centre for Child Health Research, University of Western Australia, GPO Box 855, West Perth 6872, Australia. FAU - Kolesnik, Tatiana B AU - Kolesnik TB FAU - Nicholson, Sandra E AU - Nicholson SE FAU - Prele, Cecilia M AU - Prele CM FAU - Hart, Prue H AU - Hart PH LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120407 PL - England TA - Cytokine JT - Cytokine JID - 9005353 RN - 0 (Antigens, CD) RN - 0 (CD180 protein, human) RN - 0 (DNA Primers) RN - 130068-27-8 (Interleukin-10) RN - 207137-56-2 (Interleukin-4) RN - EC 2.7.11.1 (RIPK2 protein, human) RN - EC 2.7.11.1 (Receptor-Interacting Protein Serine-Threonine Kinase 2) SB - IM MH - Animals MH - Antigens, CD/*physiology MH - Base Sequence MH - DNA Primers MH - Flow Cytometry MH - Humans MH - Inflammation/*prevention & control MH - Interleukin-10/genetics/*physiology MH - Interleukin-4/*physiology MH - Mice MH - Monocytes/*physiology MH - Real-Time Polymerase Chain Reaction MH - Receptor-Interacting Protein Serine-Threonine Kinase 2/*physiology EDAT- 2012/04/10 06:00 MHDA- 2012/08/28 06:00 CRDT- 2012/04/10 06:00 PHST- 2011/12/06 00:00 [received] PHST- 2012/02/23 00:00 [revised] PHST- 2012/03/12 00:00 [accepted] PHST- 2012/04/10 06:00 [entrez] PHST- 2012/04/10 06:00 [pubmed] PHST- 2012/08/28 06:00 [medline] AID - S1043-4666(12)00092-0 [pii] AID - 10.1016/j.cyto.2012.03.009 [doi] PST - ppublish SO - Cytokine. 2012 Jun;58(3):415-23. doi: 10.1016/j.cyto.2012.03.009. Epub 2012 Apr 7.