microRNA‐210 negatively regulates LPS‐induced production of proinflammatory cytokines by targeting NF‐κB1 in murine macrophages

Abstract

Edited by T. DalmayKeywords: microRNA NF-jB1 TLR LPS Macrophage a b s t r a c t Ligation of TLR4 with LPS in macrophages leads to the production of proinflammatory cytokines, which are central to eliminate viral and bacterial infection. However, uncontrolled TLR4 activation may contribute to pathogenesis of inflammatory diseases such as septic shock. In this study, we found microRNA-210 was induced in murine macrophages by LPS. Transfection of miR-210 mimics significantly inhibited LPS-induced production of inflammatory cytokines. In contrast, transfection of anti-miR-210 inhibitors increased LPS-induced expression of proinflammatory cytokines. Furthermore, we demonstrated that miR-210 targets NF-jB1. Therefore, our data identify miR-210 as a very important feedback negative regulator for LPS-induced production of proinflammatory cytokines.

Cutting Edge: The Transcription Factor Bob1 Counteracts B Cell Activation and Regulates miR-146a in B Cells

“…Similar to miR-146a, miR-210 is induced following B cell activation and also is expressed in other cell types. In macrophages, miR-210 appears to inhibit proinflammatory cytokines by targeting NF-kB1 (25). We also observe a 2-3-fold reduction in miR-210 levels in Bob1-deficient resting splenic B cells ( Fig.…”

MicroRNAs in the regulation of TLR and RIG-I pathways

“…62 More recently, miR-210 has also been demonstrated to be induced by LPS and target Nfkb1 mRNA. 84 Other transcription factors downstream of the TLR signaling pathway have been identified as miRNA targets. miR-17-5p and miR-20a are expressed at low levels in myeloid-derived suppresser cells and alleviate the suppressive function of myeloid-derived suppresser cells by targeting the transcription factor STAT3.…”

Identification of Novel Pretranslational Regulatory Mechanisms for NF-κB Activation

“…Based on these confidence intervals, we identified a group of microRNAs that potentially target 27 (71%) of 38 NF-B-signaling genes, as listed in Table 6A. Several of these microRNAs have been experimentally confirmed to regulate NF-B-signaling expression, such as miR-200 for RelA, miR-9/181b and Let-7 for p50, miR-125a/b for IB␣, miR-125b for Bcl-3, miR-31 for IKK␣, miR200c and miR-199 for IKK␤, miR-31 for NIK, miR-10 for Tak1, miR-16 for SMRT, and miR-19 for CYLD, respectively (21)(22)(23)(24).…”