title: Poly(ADP-ribose) polymerase 1 inhibition protects human aortic endothelial cells against LPS-induced inflammation response.
abstract: Atherosclerosis is a chronic inflammatory disease. Toll-like receptor 4 (TLR4) is an important signaling receptor and plays a critical role in the inflammatory response. Poly(ADP-ribose) polymerase 1 (PARP1) is a nuclear enzyme that can regulate the expression of various inflammatory genes. In this study, we investigated the role and the underlying mechanisms of PARP1 on lipopolysaccharide (LPS)-induced inflammation in human aortic endothelial cells. Compared with the control, LPS stimulation increased the protein expression of TLR4 and PARP1. TLR4 inhibition reduced LPS-induced upregulation of inducible nitric oxide synthase (iNOS) and ICAM-1 as well as PARP1. Nuclear factor κB (NF-κB) inhibition decreased ICAM-1 and iNOS expression. Inhibition of PARP1 decreased protein expression of inflammatory cytokines induced by LPS stimulation, probably through preventing NF-κB nuclear translocation. Our study demonstrated that LPS increased ICAM-1 and iNOS expression via TLR4/PARP1/NF-κB pathway. PARP1 might be an indispensable factor in TLR4-mediated inflammation after LPS stimulation. PARP1 inhibition might shed light on the treatment of LPS-induced inflammatory cytokines expression during atherosclerosis.
authors.affiliation: Department of thoracic surgery,  Yu Huang Ding Hospital, Yantai 264000,  China.
authors.forename: Xiaonu
authors.initials: X
authors.lastname: Peng
authors.forename: Wenjun
authors.initials: W
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
mesh_terms: D001011:Aorta / Q000166:cytology / Q000187:drug effects*; D001483:Base Sequence; D015153:Blotting, Western; D002478:Cells, Cultured; D017931:DNA Primers; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D000071137:Poly (ADP-Ribose) Polymerase-1; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D060888:Real-Time Polymerase Chain Reaction; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D017931:DNA Primers; D008070:Lipopolysaccharides; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1