Please use this identifier to cite or link to this item: http://hdl.handle.net/1822/33098

TitleDifferential post-transcriptional regulation of IL-10 by TLR2 and TLR4-activated macrophages
Author(s)Rodrigues, Fernando
Pedrosa, Jorge
Coelho, Maria Teixeira
Guedes, Joana
Ferreirinha, Pedro
Howes, Ashleigh
Lai, Wi S.
Blackshear, Perry J.
O´Garra, Anne
Castro, António G.
Saraiva, Margarida
KeywordsIL-10
MAPKs
TLRs
Post-transcriptional regulation
Issue date16-Mar-2014
PublisherWiley-Blackwell
JournalEuropean Journal of Immunology
Abstract(s)The activation of TLRs by microbial molecules triggers intracellular-signaling cascades and the expression of cytokines such as IL-10. Il10 expression is tightly controlled to ensure effective immune responses, while preventing pathology. Maximal TLR-induction of Il10 transcription in macrophages requires signaling through the MAPKs, ERK, and p38. Signals via p38 downstream of TLR4 activation also regulate IL-10 at the post-transcriptional level, but whether this mechanism operates downstream of other TLRs is not clear. We compared the regulation of IL-10 production in TLR2 and TLR4-stimulated BM-derived macrophages and found different stability profiles for the Il10 mRNA. TLR2 signals promoted a rapid induction and degradation of Il10 mRNA, whereas TLR4 signals protected Il10 mRNA from rapid degradation, due to the activation of Toll/IL-1 receptor domain-containing adaptor inducing IFN-ß (TRIF) and enhanced p38 signaling. This differential post-transcriptional mechanism contributes to a stronger induction of IL-10 secretion via TLR4. Our study provides a molecular mechanism for the differential IL-10 production by TLR2- or TLR4-stimulated BMMs, showing that p38-induced stability is not common to all TLR-signaling pathways. This mechanism is also observed upon bacterial activation of TLR2 or TLR4 in BMMs, contributing to IL-10 modulation in these cells in an infection setting.
TypeArticle
URIhttp://hdl.handle.net/1822/33098
DOI10.1002/eji.201343734
ISSN0014-2980
Publisher versionhttp://onlinelibrary.wiley.com/doi/10.1002/eji.201343734/full
Peer-Reviewedyes
AccessOpen access
Appears in Collections:ICVS - Artigos em Revistas Internacionais com Referee

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