title: Inflammatory response of monocytes to ambient particles varies by highway proximity.
abstract: Epidemiological studies have demonstrated associations of chronic respiratory disease with near-roadway pollutant exposure, effects that were independent of those of regional air pollutants. However, there has been limited study of the potential mechanisms for near-roadway effects. Therefore, we examined the in vitro effect of respirable particulate matter (PM) collected adjacent to a major Los Angeles freeway and at an urban background location. PM was collected on filters during two consecutive 15-day periods. Oxidative stress and inflammatory response (intracellular reactive oxygen species [ROS], IL-1β, IL-6, IL-8, and TNF-α) to PM aqueous extract was assessed in THP-1 cells, a model for evaluating monocyte/macrophage lineage cell responses. The near-roadway PM induced statistically significantly higher levels of IL-6, IL-8, and TNF-α (P < 0.01) and a near significant increase in IL-1β (P = 0.06) but did not induce ROS activity (P = 0.17). The contrast between urban background and near-roadway PM-induced inflammatory cytokines was similar in magnitude to that corresponding to temporal differences between the two collection periods. PM-induced proinflammatory protein expression was attenuated by antioxidant pretreatment, and PM stimulation enhanced the activity of protein kinases, including extracellular signal-regulated kinase and c-Jun N-terminal kinase. Pretreatment of THP-1 cells with kinase inhibitors reduced PM-induced proinflammatory mediator expression. The proinflammatory response was also reduced by pretreatment with polymyxin B, suggesting a role for endotoxin. However, the patterns of PM-induced protein kinase response and the attenuation of inflammatory responses by antioxidant or polymyxin B pretreatment did not vary between near-roadway and urban background locations. We conclude that near-roadway PM produced greater inflammatory response than urban background PM, a finding consistent with emerging epidemiologic findings, but these differences were not explained by PM endotoxin content or by MAPK pathways. Nevertheless, THP-1 cells may be a model for the development of biologically relevant metrics of long-term spatial variation in exposure for study of chronic disease.
authors.affiliation: 1 School of Public Health, Xinxiang Medical University, Henan Province, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Wu
authors.forename: Robin
authors.initials: R
authors.lastname: Muller
authors.forename: Kiros
authors.initials: K
authors.lastname: Berhane
authors.forename: Scott
authors.initials: S
authors.lastname: Fruin
authors.forename: Feifei
authors.initials: F
authors.lastname: Liu
authors.forename: Ilona
authors.initials: I
authors.lastname: Jaspers
authors.forename: David
authors.initials: D
authors.lastname: Diaz-Sanchez
authors.forename: David B
authors.initials: DB
authors.lastname: Peden
authors.forename: Rob
authors.initials: R
authors.lastname: McConnell
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D045744:Cell Line, Tumor; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D018986:Motor Vehicles; D018384:Oxidative Stress; D052638:Particulate Matter / Q000633:toxicity*
chemical_list: D000393:Air Pollutants; D016209:Interleukin-8; D008070:Lipopolysaccharides; D052638:Particulate Matter
keywords: epidemiology; exposure assessment; inflammation; oxidative stress; traffic-related air pollution