MicroRNA-182 supplies negative feedback regulation to ameliorate lipopolysaccharide-induced ALI in mice by targeting TLR4.

Abstract

Acute lung injury (ALI), characterized by increased excessive pulmonary inflammation, is a pervasive inflammatory disease with clinically high incidence. MicroRNA (miRNAs) have been associated with the progression of multiple diseases and are regarded as novel regulators of inflammation. However, it remains largely unknown whether the miRNAs-mediated regulatory mechanism has an effect on lipopolysaccharide (LPS)-induced inflammation in ALI. We discovered that miR-182 distinctly lessened expression in the lung tissue of mice with ALI and macrophages stimulated by LPS. We also found that overexpression of miR-182 significantly cut down the secretion of inflammatory cytokines, while this change was reversed by inhibition of miR-182. In addition, miR-182 suppressed the activation of NF-κB by targeting TLR4 expression. And it was confirmed that miR-182 directly regulated TLR4 expression at the posttranscriptional level by binding to the 3'-UTR of TLR4. Together, these data suggested that inhibition of TLR4 expression assuaged LPS-stimulated inflammation through negative feedback regulation of miR-182.