Microrna-21 inhibits lipopolysaccharide-induceacute lung injury by targeting nuclear factor-κb

Abstract

Acute lung injury (ALI) is a frequent, but severe complication following sepsis in patients with critical illness. The present study aimed to investigate the potential role of microRNA-21 (miR-21) in the regulation of inflammation in the ALI induced by lipopolysaccharide (LPS) in vitro and in vivo. The levels of inflammatory cytokines, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β and IL-10, and the level of miR-21 expression were measured in the lungs of LPS-induced ALI rats and NR8383 alveolar macrophages (AMs). To confirm the regulatory effect of miR-21 in the inflammatory reactions of ALI, NR8383 cells were transfected with a mimic of miR-21 or an anti-miR-21 inhibitor, and the subsequent changes of the miR-21 level and the levels of inflammatory cytokines were detected. The underlying molecular mechanism was also investigated. LPS-induced ALI in rats resulted in significant overexpression of pro-inflammatory cytokines, TNF-α, IL-6 and IL-1β, and miR-21, but reduced the expression of the anti-inflammatory cytokine IL-10. LPS treatment also led to a higher expression level of miR-21 and increased secretion of pro-inflammatory cytokines in NR8383 cells in a time-dependent manner. Manipulation with the miR-21 mimic significantly suppressed the LPS-mediated induction of TNF-α, IL-6 and IL-1β in NR8383 cells, while that induction was upregulated when miR-21 expression was silenced via transfection with the anti-miR-21 inhibitor. Further mechanism experiments revealed that miR-21 regulates LPS-induced inf lammation responses via the Toll-like receptor 4 and nuclear factor-κB (Nf-κB) signaling pathway. miR-21 negatively regulates inflammatory responses in LPS-induced ALI by targeting the NF.kB signaling pathway, providing further insight into the molecular mechanism of ALI progression.