Protective effects of TRPV4 inhibitor on acute lung injury induced by lipopolysaccharide in mice

Abstract

Objective To investigate the role of transient receptor potential vanilloid 4 (TRPV4) in the pathophysiology of acute lung injury (ALI) induced by lipopolysaccharide (LPS) in mice. Methods ALI model was established by intraperitoneal injection of LPS.Female 6-8 weeks old BALB/c mice were randomly divided into four groups: control group, LPS group, LPS+ GSK2193874 group and LPS+ DMSO group.The wet/dry weight ratio of lung and white blood cell count in bronchoalveolar lavage fluid (BALF) were detected.Interleukins-6 (IL-6), IL-1β, tumor necrosis factor-α, and IL-18 in lung tissue and BALF were detected by enzyme linked immunosorbent assay.Immunohistochemistry and Western blot were used to detect the expression of TRPV4 in lung tissue. Results Compared with control group, the expression of TRPV4 was increased in the lung tissue of LPS group.GSK2193874, TRPV4 specific inhibitor, could alleviate lung inflammation induced by LPS, reduce the count of white blood cells in BALF, the wet/dry weight ratio of lung, and decrease the levels of IL-6, IL-1β, tumor necrosis factor-α, IL-18 in BALF and lung tissue. Conclusions Blockade of TRPV4 signaling can attenuate the inflammation of ALI/acute respiratory distress syndrome and TRPV4 may become a new target for ALI therapy in the future. Key words: Lipopolysaccharide; Acute lung injury; Transient receptor potential vanilloid 4; GSK2193874