DUSP8 inhibits LPS-induced acute lung injury by regulating macrophage response

Background:Although many studies focus on investigating the new therapeutic target of acute lung injury(ALI),there still needs more works on exploring the role of other molecular in the pathology of ALI.Dual specificity phosphatase(DUSP)8 has been reported to participate in the process of tumor.However,the potential role of DUSP8 in lipopolysaccharide(LPS)-induced murine ALI is still unclear.Methods:Firstly,murine ALI was established by LPS treatment and further measured by hematoxylin-eosin staining.Next,the expression of DUSP8 in lung tissues was analyzed by real-time polymerase chain reaction.Then,DUSP8 overexpression vector was utilized and the protein level of DUSP8 was detected by western blot.Moreover,the pathologic injury was measured by hematoxylin-eosin staining and wet/dry ratio.Meanwhile,we cultured bone-marrow-derived macrophages and detected the expression of DUSP8 by real-time polymerase chain reaction and western blot after LPS treatment.In addition,DUSP8 overexpression vector was transfected into bone-marrow-derived macrophages and the levels of related inflammatory cytokines were measured by enzyme-linked immunosorbent assay.Results:Compared with the control mice,DUSP8 significantly decreased in LPS-induced murine ALI.Next,DUSP8 overexpression could attenuate the pathology of ALI by altering lung inflammation and edema.Meanwhile,DUSP8 was also reduced in LPS-treated BMDM and reached a peak at 12h.Besides,DUSP8 overexpression could reduce the productions of related inflammatory cytokines,such as interleukin-1β,tumor necrosis factor-αand interleukin-6 in LPS-treated bone-marrow-derived macrophages.Conclusion:DUSP8 is reduced in LPS-induced murine acute lung injury and DUSP8 overexpression could ameliorate the pathologic injury of ALI by altering macrophage inflammation responses.