Utilize este identificador para referenciar este registo:
https://hdl.handle.net/1822/33098
Título: | Differential post-transcriptional regulation of IL-10 by TLR2 and TLR4-activated macrophages |
Autor(es): | 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 |
Palavras-chave: | IL-10 MAPKs TLRs Post-transcriptional regulation |
Data: | 16-Mar-2014 |
Editora: | Wiley-Blackwell |
Revista: | European Journal of Immunology |
Resumo(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. |
Tipo: | Artigo |
URI: | https://hdl.handle.net/1822/33098 |
DOI: | 10.1002/eji.201343734 |
ISSN: | 0014-2980 |
Versão da editora: | http://onlinelibrary.wiley.com/doi/10.1002/eji.201343734/full |
Arbitragem científica: | yes |
Acesso: | Acesso aberto |
Aparece nas coleções: | ICVS - Artigos em revistas internacionais / Papers in international journals |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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teixeira-coelho_eur j imm_2014 posp.pdf | 797,96 kB | Adobe PDF | Ver/Abrir |