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.
Department of Intensive Care Unit, Qilu Hospital of Shandong University, Jinan 250012, China Department of Intensive Care Unit, Yu Huang Ding Hospital, Yantai 264000, China.
Jing
J
Wang
Department of Intensive Care Unit, Yu Huang Ding Hospital, Yantai 264000, China.
Luyi
L
Liu
Department of Intensive Care Unit, Yu Huang Ding Hospital, Yantai 264000, China.
Yonghong
Y
Xia
Department of Intensive Care Unit, Qilu Hospital of Shandong University, Jinan 250012, China dwwu55@sina.com.
Dawei
D
Wu
D001483:Base Sequence; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism*; D004249:DNA Damage; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D020868:Gene Silencing; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D018384:Oxidative Stress; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics*; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013314:Stress, Mechanical
D016207:Cytokines; D017931:DNA Primers; D018836:Inflammation Mediators; D034741:RNA, Small Interfering; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases
NF-κB; asthma; inflammatory factor; mechanical stretch; poly(ADP-ribose) polymerase-1