Silencing of poly(ADP-ribose) polymerase-1 suppresses hyperstretch-induced expression of inflammatory cytokines in vitro.

In addition to biochemical stimuli, physical forces also play a critical role in regulating the structure, function, and metabolism of the lung. Hyperstretch can induce the inflammatory responses in asthma, but the mechanism remains unclear. Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme that can regulate a variety of inflammatory cytokines expression. In the present study, we aimed to investigate the role and mechanism of PARP-1 in mechanical stretch-induced inflammation in human bronchial epithelial cells (HBEpiCs). HBEpiCs were simulated by mechanical stretch and cells under static were used as the control. PARP-1 expression was interfered by small interfering RNA. Oxidative stress was evaluated by DHE staining. DNA damage was assessed by comet assay. The results showed that interleukin-8 (IL-8) and vascular cell adhesion molecule-1 (VCAM-1) expression were regulated by hyperstretch in a time-dependent manner. Hyperstretch could increase PARP-1 expression and activity by inducing superoxide production and DNA damage. Silencing of PARP-1 attenuated hyperstretch-induced IL-8 and VCAM-1 up-regulation as well as monocytes adhesion, which were related to the inhibition of nuclear factor-kappa B (NF-κB) translocation. Our study showed that hyperstretch could induce inflammatory response and superoxide production as well as DNA damage in HBEpiCs. PARP-1 silencing decreased IL-8 and VCAM-1 expression, partly through inhibition of NF-κB translocation. PARP-1 played a fundamental role in hyperstretch-induced inflammation. PARP-1 silencing could be used as a potential therapeutic approach to reverse bronchial epithelial inflammation in asthma.