Poly(ADP-ribose) Polymerase1Inhibition Protects Human Bronchial Endothelial Cells Against Nicotine-induced Inflammation Response

ObjectiveTo detect the changes of bronchial epithelial cells inflammatory cytokine stimulated by nicotine and to investigate the function and mechanism of poly(ADP-ribose) polymerase1(PARP1) inhibition in the inflammatory response induced by nicotine and mediated by toll-like receptor4(TLR4).Materials and MethodsCultivated bronchial epithelial cells were prepared. The expression of inflammatory cytokine related gene and protein of nicotine stimulation group, TLR4and PARP1inhibition group were detected separately togather with their relative negtive control groups by quantitative reverse transcript-polymerase chain reaction (RT-PCR), western bloting, small interference RNA (siRNA) and immunofluorescence.ResultsCompared with the control, nicotine stimulation increased the protein expression of TLR4and PARP1. TLR4inhibition reduced nicotine induced upregulation of inducible nitric oxide synthase (iNOS) and intercellular adhesion molecule1(ICAM-1) as well as PARP1. Nuclear factor-kappaB (NF-κB) inhibition decreased ICAM-1and iNOS expression. Inhibition of PARP1decreased protein expression of inflammatory cytokines induced by nicotine stimulation, probably through preventing NF-κB nuclear translocation.ConclusionsOur study demonstrated that nicotine increased ICAM-1and iNOS expression via TLR4/PARP1/NF-κB pathway. PARP1might be a dispensable factor in TLR4 mediated inflammation after nicotine stimulation. PARP1inhibition might shed a light on the treatment of nicotine induced inflammatory cytokines expression during bronchial epithelium atypical heperplasia.