Wang, ZhuoFilgueiras, LucianoWang, SuonjanSerezani, Ana Paula MoreiraPeters-Golden, MarcJancar, SoniaSerezani, C. Henrique2016-06-282016-06-282014-03-01Wang, Z., Filgueiras, L., Wang, S., Serezani, A. P. M., Peters-Golden, M., Jancar, S., & Serezani, C. H. (2014). Leukotriene B4 enhances the generation of pro-inflammatory microRNAs to promote MyD88-dependent macrophage activation. Journal of Immunology (Baltimore, Md. : 1950), 192(5), 2349–2356. http://doi.org/10.4049/jimmunol.1302982https://hdl.handle.net/1805/10199MicroRNAs are known to control TLR activation in phagocytes. We have shown that leukotriene (LT) B4 (LTB4) positively regulates macrophage MyD88 expression by decreasing suppressor of cytokine signaling-1 (SOCS-1) mRNA stability. In this study, we investigated the possibility that LTB4 control of MyD88 expression involves the generation of microRNAs. Our data show that LTB4, via its receptor B leukotriene receptor 1 (BLT1) and Gαi signaling, increased macrophage expression of inflammatory microRNAs, including miR-155, miR-146b, and miR-125b. LTB4-mediated miR-155 generation was attributable to activating protein-1 activation. Furthermore, macrophage transfection with antagomirs against miR-155 and miR-146b prevented both the LTB4-mediated decrease in SOCS-1 and increase in MyD88. Transfection with miR-155 and miR-146b mimics decreased SOCS-1 levels, increased MyD88 expression, and restored TLR4 responsiveness in both wild type and LT-deficient macrophages. To our knowledge, our data unveil a heretofore unrecognized role for the GPCR BLT1 in controlling expression of microRNAs that regulate MyD88-dependent activation of macrophages.en-USPublisher PolicyGTP-Binding Protein alpha SubunitsGene Expression RegulationInflammationLeukotriene B4Macrophages, PeritonealMicroRNAsMyeloid Differentiation Factor 88Receptors, Leukotriene B4Signal TransductionSuppressor of Cytokine Signaling ProteinsArticle