Role Of MicroRNA-155 In Smoke Inhalation-induced Acute Lung Injury

Objective:Smoke inhalation-induced acute lung injury?ALI?is a critical illness with high mortality.It's also a major cause of death among fire victims.However,research on the pathogenesis of smoke inhalation-induced ALI remains scarce.Accumulating evidence indicates that micro RNA-155?mi R-155?and suppressor of cytokine signaling 1?SOCS-1?are involved in pulmonary inflammatory response.Our research aims to investigate the role and mechanism of mi R-155 in smoke-induced ALI.Methods:Real-time quantitative PCR was used to determine the expression levels of mi R-155 in lung tissue at indicated time periods after smoke inhalation.The association between mi R-155 and lung injury severity was explorered through pathological observation and lung injury scoring which were performed among wild type?WT?and mi R-155 knockout(mi R-155^-/-)mice following smoke inhalation.Bronchoalveolar lavage fluid?BALF?and lung tissue were collected from WT and mi R-155^–/–mice.Then differential leukocyte count and measurements of macrophage inflammatory protein 2?MIP-2?,keratinocyte chemoattractant?KC?and myeloperoxidase?MPO?were performed to explore the role of mi R-155 in pulmonary neutrophil activation and accumulation.SOCS-1 m RNA and protein levels were measured by PCR and immunoblotting to investigate the regulation of mi R-155 on SOCS-1 expression.SOCS-1 was silenced in mi R-155^–/–pulmonary neutrophils by small interfering RNA?si RNA?transfection.KC and MIP-2 levels were analyzed by ELISA following smoke exposure to explore the mechanism by which mi R-155modulates pulmonary neutrophil activation and recruitment through SOCS-1.Results:?1?Mi R-155 expression was up-regulated and culminated at around 12 h following smoke inhalation.?2?Edema,hyperemia,exudation and neutrophil infiltration in lung tissue and lung injury score were significantly alleviated in mi R-155^-/-mice after smoke inhalation.?3?Neutrophil count in BALF,MPO level,KC and MIP-2 expression were significantly decreased in mi R-155^-/-mice after smoke inhalation.?4?Both m RNA and protein expression of SOCS-1 were increased in mi R-155^-/-mice lung tissue and pulmonary neutrophils after smoke exposure.?5?Lack of SOCS-1 enhanced KC and MIP-2 production.SOCS-1 silencing reversed the inhibition of chemokines expression caused by mi R-155 knockout.Conclusions:?1?Smoke inhalation induces mi R-155 expression in lung tissue.?2?Mi R-155 participates in pulmonary inflammatory response of smoke inhalation-induced ALI.Mi R-155 knockout attenuates lung tissue injury.?3?Smoke-induced mi R-155 inhibits SOCS-1 protein expression by m RNA degradation.?4?In the pathogenesis of smoke-induced ALI,mi R-155 modulates pulmonary neutrophil activation and recruitment by promoting KC and MIP-2 expression through down-regulation of SOCS-1.It was demonstrated that,for the first time,mi R-155 is involved in the pathogenesis of smoke-induced ALI in the present study.It was preliminarily revealed that mi R-155 regulates the activation and recruitment of pulmonary neutrophils by inhibiting SOCS-1,which provides further evidence for the development of mi R-155as a novel target for the therapeutic drug of ALI.