Olaparib regulates inflammatory response in lipopolysaccharide-induced A549 cells through PARP-1 pathway / 中国药理学与毒理学杂志

ABSTRACT

OBJECTIVE To investigate the protective effect of olaparib on the inflammatory damage to alveolar epithelial cells induced by lipopolysaccharide (LPS). METHODS The alveolar epithelial cells (A549) were cultured in vitro and incubated with LPS 10 mg-L-1 and olaparib 10 and 25 μmol-L-1 for 24 h. The levels of cytokines interleukin 6 (IL-6), IL-8, and IL-10 were detected by enzyme linked immunosorbent assay (ELISA), the mRNA expression levels of TNF-α, IL-1β, IL-6, IL-8, and ICAM-1 were analyzed by real-time PCR, the level of ROS was analyzed by flow cytometry, and the expression of poly (ADP-ribose) polymerase-1 (PARP-1) and phosphorylation of proteins involved in NF-ΚB signaling pathway in cells were detected by Western blotting. RESULTS Compared with LPS 10 mg-L-1 injury group, olaparib 10 and 25 μmol·L-1 could significantly reduce the release of IL-6, IL-8 and ROS levels in A549 cells induced by LPS (P<0.01), and increase the release of IL-10 (P<0.01). Olaparib 10 and 25 μmol·L-1 could also inhibit the mRNA expressions of TNF-α, IL-1β, IL-6, IL-8, and ICAM-1 (P<0.01), and inhibit the expression of PARP-1 and phosphorylation proteins involved in NF-ΚB signaling pathway induced by LPS (P<0.01). CONCLUSION Olaparib has some protective effect on inflammatory damage and oxidative stress in alveolar epithelial cells induced by LPS, and the mechanism may be that it inhibits the expression and release of cytokines by down-regulating the expression of PARP-1 and subsequently affecting the activation of the NF-ΚB pathway.