Downregulated expression of miR-223 promotes Toll-like receptor-activated inflammatory responses in macrophages by targeting RhoB

Toll-like receptors (TLRs) induced-inflammatory response must be tightly regulated to avoid impairment in host itself. Numerous factors have been identified in regulation of TLR-triggered inflammatory response. Among these, microRNAs (miRNAs) are small non-coding RNA molecules which have got much attention. M1R-223, which highly expresses in myeloid cells of the bone marrow, has reported to participate in kinds of inflammatory responses by targeting inflatrunasome sensor-NLRP3 to repress production of IL-6 and IL-1 beta, and thus attenuate inflammatory response. However, the function of miR-223 in TLRs-activated inflammatory response of macrophages is not clear. Here we found miR-223 expression is dramatically reduced in macrophages by TLR ligand stimulation (e.g. LPS, CpG and poly (I:C)). The down-regulated miR-223 leads to the increase in the RhoB expression, which induce the activation of NF-kappa B and MAPK signaling, promoting TNF-alpha, IL-6 and IL-1 beta production upon LPS stimulation. In addition, the histone deacetylase inhibitor trichostatin A increased miR-223 expression obviously in TLR-triggered macrophages, which in turn suppressed RhoB expression and downstream IL-6 production, suggesting that the inhibition of miR-223 by histone deacetylation may be involved in the regulation of TLR-activated inflammatory response. Herein, our findings suggest that miR-223-RhoB axis might be a novel target for the treatment of inflammatory diseases.