Leukotriene B-4 Enhances the Generation of Proinflammatory MicroRNAs To Promote MyD88-Dependent Macrophage Activation

作者：Wang Zhuo; Filgueiras Luciano Ribeiro; Wang Soujuan; Serezani Ana Paula Moreira; Peters Golden Marc; Jancar Sonia; Serezani C Henrique^*

来源：The Journal of Immunology, 2014, 192(5): 2349-2356.

DOI：10.4049/jimmunol.1302982

MicroRNAs are known to control TLR activation in phagocytes. We have shown that leukotriene (LT) B-4 (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 G alpha i 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.

• 出版日期2014-3-1