miR-27a Regulates Inflammatory Response of Macrophages by Targeting IL-10

Página do item simplificado
dc.contributor.authorXie, Na
dc.contributor.authorCui, Huachun
dc.contributor.authorBanerjee, Sami
dc.contributor.authorTan, Zheng
dc.contributor.authorSalomao, Reinaldo [UNIFESP]
dc.contributor.authorFu, Mingui
dc.contributor.authorAbraham, Edward
dc.contributor.authorThannickal, Victor John
dc.contributor.authorLiu, Gang
dc.contributor.institutionUniv Alabama Birmingham
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionUniv Missouri
dc.contributor.institutionWake Forest Sch Med
dc.date.accessioned2016-01-24T14:37:30Z
dc.date.available2016-01-24T14:37:30Z
dc.date.issued2014-07-01
dc.description.abstractAlthough microRNAs were shown to participate in innate immune responses, it is not completely understood how they regulate negative immunomodulatory events. IL-10 is an important anti-inflammatory mediator that prevents excessive inflammation and associated immunological pathologies. Although the regulation of IL-10 expression has been well studied at both the transcriptional and translational levels, it is less clear how microRNAs control IL-10 expression during inflammation. in this study, we found that miR-27a is downregulated in macrophages following stimulation through TLR2 and TLR4, but not TLR3. Upregulation of miR-27a enhanced the expression of proinflammatory cytokines in TLR2/4-activated macrophages. Conversely, knockdown of miR-27a diminished cytokine expression. Mechanistically, we found that miR-27a negatively regulates IL-10 expression; upregulation of miR27a decreases, whereas downregulation of miR-27a increases, IL-10 expression in activated macrophages. Likely due to the decreased expression of IL-10, upregulation of miR-27a diminished IL-10-dependent STAT3 phosphorylation in TLR4-activated macrophages. Consistent with IL-10 being a potential mediator for the role of miR-27a in the immune response, blocking IL-10 abolished the enhancing effect of miR-27a on TLR4-activated inflammation. in conclusion, our study identified miR-27a downregulation as a negative-regulatory mechanism that prevents overly exuberant TLR2- and TLR4-driven inflammatory responses.en
dc.description.affiliationUniv Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA
dc.description.affiliationUniversidade Federal de São Paulo, Paulista Sch Med, Dept Med, BR-04039032 São Paulo, Brazil
dc.description.affiliationUniv Missouri, Dept Basic Med Sci, Kansas City, MO 64108 USA
dc.description.affiliationWake Forest Sch Med, Winston Salem, NC 27157 USA
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Paulista Sch Med, Dept Med, BR-04039032 São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipNational Institutes of Health
dc.description.sponsorshipIDNational Institutes of Health: HL114470
dc.description.sponsorshipIDNational Institutes of Health: HL105473
dc.description.sponsorshipIDNational Institutes of Health: HL076206
dc.format.extent327-334
dc.identifierhttp://dx.doi.org/10.4049/jimmunol.1400203
dc.identifier.citationJournal of Immunology. Bethesda: Amer Assoc Immunologists, v. 193, n. 1, p. 327-334, 2014.
dc.identifier.doi10.4049/jimmunol.1400203
dc.identifier.issn0022-1767
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/37911
dc.identifier.wosWOS:000338438900038
dc.language.isoeng
dc.publisherAmer Assoc Immunologists
dc.relation.ispartofJournal of Immunology
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titlemiR-27a Regulates Inflammatory Response of Macrophages by Targeting IL-10en
dc.typeinfo:eu-repo/semantics/article
Arquivos
Coleções
EPM - Artigos