Poly(ADP-ribose) polymerase 1 inhibition protects human aortic endothelial cells against LPS-induced inflammation response.

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.