title: Kinetic analysis of cytokine response to cigarette smoke condensate by human endothelial and monocytic cells.
abstract: Atherosclerosis is generally considered an inflammatory disease characterized by the accumulation of lipid in large and medium elastic arteries. Individuals who smoke are at increased risk for developing atherosclerosis and the clinical events associated with this disease. Underlying the mechanisms involved in atherosclerotic lesion development exists a complex pattern of signaling, involving molecules (cytokines and chemokines) that mediate the progression of arterial lesions. The unique nature of exposure to tobacco-related toxicants during the process of smoking prompted our investigation of the time-dependent responses of two critical cell types to cigarette smoke condensate exposure. In this study, we examined the kinetic responses, using suspension array technology and RT-PCR of 17 cytokines (IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17 GM-CSF, G-CSF, INF-gamma, TNF-alpha, MCP-1 and MIP-1beta) in human aortic endothelial cells (HAECs) and THP-1 monocyte macrophages following exposure to cigarette smoke condensate (CSC) for 24h. In HAECs, IL-8 and IL-4 were rapidly stimulated by CSC exposure while, surprisingly, MCP-1 expression was downregulated. In THP-1 macrophages, IL-6, MIP-1beta, MCP-1 and IL-1beta protein expression were suppressed upon CSC exposure. All other measurable cytokines in THP-1 cells exposed to CSC had levels of protein and mRNA similar to controls. Depending on cell type, CSC uniquely influences the expression of cytokines. The complex interplay of these signaling molecules within the framework of atherosclerosis points to the ability of cigarette smoke components to alter such signaling following acute exposure, and by this mechanism may alter the course of both atherogenesis initiation and progression.
authors.affiliation: Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157-1083, USA.
authors.forename: Brian K
authors.initials: BK
authors.lastname: Nordskog
authors.forename: Wanda R
authors.initials: WR
authors.lastname: Fields
authors.forename: Gary M
authors.initials: GM
authors.lastname: Hellmann
mesh_terms: D001011:Aorta; D002460:Cell Line; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012906:Smoke; D013997:Time Factors; D014026:Nicotiana
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D012906:Smoke