{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T15:56:58Z","timestamp":1772639818640,"version":"3.50.1"},"reference-count":50,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,12,16]],"date-time":"2013-12-16T00:00:00Z","timestamp":1387152000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2014,3]]},"abstract":"The activation of TLR<\/jats:styled-content>s by microbial molecules triggers intracellular\u2010signaling cascades and the expression of cytokines such as IL<\/jats:styled-content>\u201010. Il10<\/jats:italic> expression is tightly controlled to ensure effective immune responses, while preventing pathology. Maximal TLR<\/jats:styled-content>\u2010induction of Il10<\/jats:italic> transcription in macrophages requires signaling through the MAPK<\/jats:styled-content>s, ERK,<\/jats:styled-content> and p38. Signals via p38 downstream of TLR<\/jats:styled-content>4 activation also regulate IL<\/jats:styled-content>\u201010 at the post\u2010transcriptional level, but whether this mechanism operates downstream of other TLR<\/jats:styled-content>s is not clear. We compared the regulation of IL<\/jats:styled-content>\u201010 production in TLR<\/jats:styled-content>2 and TLR<\/jats:styled-content>4\u2010stimulated BM<\/jats:styled-content>\u2010derived macrophages and found different stability profiles for the Il10<\/jats:italic> mRNA<\/jats:styled-content>. TLR<\/jats:styled-content>2 signals promoted a rapid induction and degradation of Il10<\/jats:italic> mRNA<\/jats:styled-content>, whereas TLR<\/jats:styled-content>4 signals protected Il10<\/jats:italic> mRNA from rapid degradation, due to the activation of T<\/jats:styled-content>oll\/IL<\/jats:styled-content>\u20101 receptor domain\u2010containing adaptor inducing IFN<\/jats:styled-content>\u2010\u03b2 (TRIF<\/jats:styled-content>) and enhanced p38 signaling. This differential post\u2010transcriptional mechanism contributes to a stronger induction of IL<\/jats:styled-content>\u201010 secretion via TLR<\/jats:styled-content>4. Our study provides a molecular mechanism for the differential IL<\/jats:styled-content>\u201010 production by TLR<\/jats:styled-content>2\u2010 or TLR<\/jats:styled-content>4\u2010stimulated BMM<\/jats:styled-content>s, showing that p38\u2010induced stability is not common to all TLR<\/jats:styled-content>\u2010signaling pathways. This mechanism is also observed upon bacterial activation of TLR<\/jats:styled-content>2 or TLR<\/jats:styled-content>4 in BMM<\/jats:styled-content>s, contributing to IL<\/jats:styled-content>\u201010 modulation in these cells in an infection setting.<\/jats:p>","DOI":"10.1002\/eji.201343734","type":"journal-article","created":{"date-parts":[[2013,11,13]],"date-time":"2013-11-13T23:08:00Z","timestamp":1384384080000},"page":"856-866","source":"Crossref","is-referenced-by-count":45,"title":["Differential post\u2010transcriptional regulation of IL<\/scp>\u201010 by TLR<\/scp>2 and TLR<\/scp>4\u2010activated macrophages"],"prefix":"10.1002","volume":"44","author":[{"given":"Maria","family":"Teixeira\u2010Coelho","sequence":"first","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS) School of Health Sciences University of Minho Braga Portugal"},{"name":"ICVS\/3B's \u2013 PT Government Associate Laboratory Braga\/Guimar\u00e3es 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