title: Nicotine induces the expression of C-reactive protein via MAPK-dependent signal pathway in U937 macrophages.
abstract: Atherosclerosis is an inflammatory disease in the vessel wall. Nicotine, a major component of cigarette smoke, is an independent risk factor for cardiovascular diseases including atherosclerosis. As an inflammatory molecule, C- reactive protein (CRP) participates in atherogenesis. Although it has been confirmed that CRP level in smoking patient is significantly higher than non-smokers and cigarette withdrawal, it is unknown whether nicotine induces CRP expression in macrophages. The present study was to observe effect of nicotine on CRP production and the related signal pathway in U937 macrophages. The results showed that nicotine significantly increased mRNA and protein expression of CRP in U937 macrophages in time- and concentration-dependent ways. Nicotinic acetylcholine receptor (nAChR) blocker hexamethonium, MEK1/2 inhibitor PD98059, p38 MAPK inhibitor SB203580 and NF-κB inhibitor PDTC almost completely abolished nicotineinduced CRP expression in mRNA and protein levels in U937 macrophages. The further study indicated that hexamethonium, PD98059, and SB203580 significantly inhibited ERK1/2 and p38 MAPK phosphorylation. These demonstrate that nicotine has ability to induce CRP expression in macrophages through nAChR-ERK1/2/p38 MAPK-NF-κB signal pathway, which contributes to better understanding of the pro-inflammatory and pro-atherosclerotic effects of nicotine in cigarette smokers.
authors.affiliation: Department of Pharmacology, Xi'an Jiaotong University School of Medicine, Xi'an, PR China.
authors.forename: Junjun
authors.initials: J
authors.lastname: Mao
authors.forename: Juntian
authors.initials: J
authors.lastname: Liu
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Pang
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.forename: Jinyan
authors.initials: J
authors.lastname: Song
authors.forename: Chunjie
authors.initials: C
authors.lastname: Han
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.forename: Shuyue
authors.initials: S
authors.lastname: Wang
mesh_terms: D050197:Atherosclerosis / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D020935:MAP Kinase Signaling System; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D007093:Imidazoles; D016328:NF-kappa B; D011725:Pyridines; D011978:Receptors, Nicotinic; D009538:Nicotine; D002097:C-Reactive Protein; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580