| First Author | Wang Z | Year | 2014 |
| Journal | J Immunol | Volume | 192 |
| Issue | 5 | Pages | 2349-56 |
| PubMed ID | 24477912 | Mgi Jnum | J:209817 |
| Mgi Id | MGI:5568788 | Doi | 10.4049/jimmunol.1302982 |
| Citation | Wang Z, et al. (2014) Leukotriene B4 enhances the generation of proinflammatory microRNAs to promote MyD88-dependent macrophage activation. J Immunol 192(5):2349-56 |
| abstractText | MicroRNAs 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 Galphai 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. |
