title: Induction of proinflammatory cytokines and C-reactive protein in human macrophage cell line U937 exposed to air pollution particulates.
abstract: Exposure to particulate matter air pollution causes inflammatory responses and is associated with the progression of atherosclerosis and increased cardiovascular mortality. Macrophages play a key role in atherogenesis by releasing proinflammatory cytokines and forming foam cells in subendothelial lesions. The present study quantified the inflammatory response in a human macrophage cell line (U937) after exposure to an ambient particulate sample from urban dust (UDP) and a diesel exhaust particulate (DEP). The effect of native UDP and DEP was compared with their corresponding organic extracts (OE-UDP/OE-DEP) and stripped particles (sUDP/sDEP) to clarify their respective roles. Exposure to OE-UDP, OE-DEP, UDP, DEP, and 2,3,7,8-tetrachlorodibenzo-p-dioxin led to a greater increase of interleukin (IL)-8, tumor necrosis factor-alpha, and cyclooxygenase-2 mRNA expression than did the stripped particles, whereas sUDP, sDEP, UDP, and DEP led to a greater production of C-reactive protein and IL-6 mRNA. The particles and the organic extract-induced expression of cyclooxygenase-2 and cytochrome P450 (CYP)1a1 was significantly suppressed by co-treatment with an aryl hydrocarbon receptor (AhR) antagonist, indicating that these effects are mainly mediated by the organic components, which can activate the AhR and CYP1a1. In contrast, the induction of C-reactive protein and IL-6 seems to be a particle-related effect that is AhR independent. The inflammatory response induced by particulate matter was associated with a subsequent increase of cholesterol accumulation, a hallmark of foam cells. Together, these data illustrate the interaction between particulate matter and the inflammatory response as well as the formation of cholesterol-accumulating foam cells, which are early markers of cardiovascular disease.
authors.affiliation: Department of Environmental Toxicology, University of California, Davis, California 95616, USA. cfvogel@ucdavis.edu
authors.forename: Christoph Franz Adam
authors.initials: CF
authors.lastname: Vogel
authors.forename: Eric
authors.initials: E
authors.lastname: Sciullo
authors.forename: Pat
authors.initials: P
authors.lastname: Wong
authors.forename: Paul
authors.initials: P
authors.lastname: Kuzmicky
authors.forename: Norman
authors.initials: N
authors.lastname: Kado
authors.forename: Fumio
authors.initials: F
authors.lastname: Matsumura
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism; D002947:Cities; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004391:Dust; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D012333:RNA, Messenger / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D020298:U937 Cells; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D000393:Air Pollutants; D022782:CCAAT-Enhancer-Binding Protein-beta; D016207:Cytokines; D004391:Dust; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D001335:Vehicle Emissions; D002097:C-Reactive Protein; D019363:Cytochrome P-450 CYP1A1; D051546:Cyclooxygenase 2