title: NF-κB pathway mediates vascular smooth muscle response to nicotine.
abstract: Vascular smooth muscle cells (SMCs) and endothelial cells (ECs) play important roles in nicotine-induced cardiovascular disease. To elucidate the mechanism underlying the abnormal SMC behavioral response to nicotine, we investigated the activation of the NF-κB signal transduction pathway and cell adhesion molecular (CAM) expression on SMCs. Also we used different cell culture manner of SMC sole and EC-SMC co-culture with a 0.4 or a 3 μm membrane pore, to observe whether there is a crosstalk between EC/SMC involved in the process of NF-κB pathway activation. Nicotine-induced effects were observed in SMCs by both monoculture and co-culture with the 3 μm-pore size, including the phosphorylation of IKK and IκB, the shift of transcription factor NF-κB, and the enhancement of SMC cytoskeleton protein expression and migration ability, but none were observed by co-culture with the 0.4 μm-pore size. All of the actions could be distinctly blocked by α-bungarotoxin (α7 nicotinic receptor inhibitor) or PDTC (NF-κB suppressor). Flow cytometry analysis showed that the adhesion molecules ICAM-1 and LFA-1 and VCAM-1 and VLA-4 were better expressed similarly on the surface of SMCs in the monoculture and 3 μm-pore size co-culture system vs. the 0.4 μm co-culture way. The results imply that nicotine induces SMC cytoskeleton protein up-expression and migration via the NF-κB signaling pathway and that EC-SMC crosstalk via CAM facilitates its response to nicotine.
authors.affiliation: School of Life Science and Technology, Shanghai Jiao Tong University, Shanghai, PR China.
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Wang
authors.forename: Weidong
authors.initials: W
authors.lastname: Wu
authors.forename: Maoping
authors.initials: M
authors.lastname: Tang
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
authors.forename: Lianyun
authors.initials: L
authors.lastname: Wang
authors.forename: Wangjie
authors.initials: W
authors.lastname: Xu
authors.forename: Zhongdong
authors.initials: Z
authors.lastname: Qiao
mesh_terms: D002038:Bungarotoxins / Q000494:pharmacology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D018920:Coculture Techniques; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D020672:I-kappa B Proteins / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D021381:Protein Transport / Q000187:drug effects; D015398:Signal Transduction; D014471:Umbilical Veins / Q000166:cytology
chemical_list: D002038:Bungarotoxins; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D020672:I-kappa B Proteins; D016328:NF-kappa B; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D009538:Nicotine; D051550:I-kappa B Kinase