Smoke inhalation causes acute lung injury (ALI), a severe clinical disease with high mortality. Accumulating evidence indicates that microRNA-155 (miR-155) and suppressor of cytokine signaling 1 (SOCS-1), as mediators of inflammatory response, are involved in the pathogenesis of ALI. In this paper, we explored the proinflammatory mechanism of miR-155 in smoke-inhalation-induced ALI. Our data revealed that smoke inhalation induces miR-155 expression, and miR-155 knockout (KO) significantly ameliorates smoke-inhalation-induced lung injury in mice. Neutrophil infiltration and myeloperoxidase (MPO), macrophage inflammatory protein 2 (MIP-2) and keratinocyte chemoattractant (KC) expressions were decreased in miR-155-/- mice after smoke inhalation as well. Real-time RT-PCR and immunoblotting results showed that SOCS-1 level was remarkably increased in miR-155-/- mice after smoke exposure. Furthermore, the experiments performed in isolated miR-155 KO pulmonary neutrophils demonstrated that the lack of SOCS-1 enhanced inflammatory cytokines (MIP-2 and KC) secretion in response to smoke stimulation. In conclusion, smoke induces increased expression of miR-155, and miR-155 is involved in inflammatory response to smoke-inhalation-induced lung injury by inhibiting the expression of SOCS-1.
Keywords: acute lung injury; microRNA-155; neutrophils; suppressor of cytokine signaling-1.