The Role Of Fn14 Activation In Inflammation Out Of Control Of Acute Lung Injury

Objective: Acute lung injury/acute respiratory distress syndrome(ALI/ARDS)is a non-cardiogenic,acute exacerbation,and dangerous disease,characterized by dual lung infiltration,and severe hypoxemia.The mortality rate of ALI is up to 35%-46%,and there is currently no effective treatment.Recently,it has been found that Fn14 is closely related to the development of acute lung injury.However,whether its receptors participate in the development of acute lung injury has not been reported.This study is to investigate the role of Fn14 in LPS-induced ALI in mice.Methods: Acute lung injury model was established by intraperitoneal injection of amylin(20 mg/kg)for 1 h and subsequent intratracheal injection of lipopolysaccharide(5 mg/kg)for 12 h.we observed effect of blocking Fn14 on survival rate in ALI mice induced by LPS.HE staining and lung inflammation scores were used to evaluate the pathological changes of lung tissue in mice.Serum LDH activity was detected.The number of inflammatory cells in bronchoalveolar lavage fluid was measured by cell counting method.The activity of myeloperoxidase dismutase in the lung tissue was measured to reflect the infiltration of inflammatory cells in the lungs.RT-PCR was used to detect gene expression levels of IL-1?,TNF-?,MCP-1.Western blot was used to detect the expression of Fn14;ELISA was used to detect the expression of TNF-?and IL-1?in lung tissue and the expression of TNF-?,IL-1? and MCP-1 in bronchoalveolar lavage fluid.Results: Western blot showed the increase of Fn14.Blocking Fn14 with ATA by inhibiting Fn14 can increase the lethal dose of LPS-induced survival of ALI mice;Blocking Fn14 can reduce the lung pathological changes and inflammatory scores of LPS-induced ALI mice;Blocking Fn14 can reduce cell damage;Blocking Fn14 can reduce inflammatory cell infiltration;Blocking Fn14 can down-regulate the expression and secretion of pro-inflammatory cytokine TNF-? and it can also reduce the expression and secretion of monocyte chemotactic factor-1.Further studies found that blocking Fn14 can reduce the lipid peroxidation product MDA content and partially increase antioxidant enzyme SOD activity.Conclusion: 1.Fn14 activation is involved in the occurrence and development of acute lung injury;2.Blocking Fn14 can reduce ALI lung inflammation.