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Inflammatory Response of Monocytes to Ambient Particles Varies by Highway Proximity
Citation:
Wu, W., R. Muller, K. Berhane, S. Fruin, F. Liu, I. Jaspers, D. Diaz-Sanchez, D. Peden, AND R. McConnell. Inflammatory Response of Monocytes to Ambient Particles Varies by Highway Proximity. AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY. American Thoracic Society, New York, NY, 51(6):802-09, (2014).
Impact/Purpose:
Inflammatory cytokine activity after near-roadway PM challenge of a cellular model for airway macrophage response was substantially larger than the activity associated with urban background PM. Our results provide biologically plausible evidence supporting the epidemiological studies suggesting that near-road PM has increased impacts on human health.
Description:
Epidemiological studies have demonstrated associations of chronic respiratory disease with near-roadway pollutant exposure, effects which 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 fifteen day periods. Oxidative stress and inflammatory response (intracellular reactive oxygen species (ROS), IL-1β, IL-6, IL-8 and TNFα) 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 TNFα (P<0.01), and a near significant increase in IL-1β (P=0.06), but not 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 pro-inflammatory protein expression was attenuated by antioxidant pre-treatment, and PM stimulation enhanced activity of protein kinases including extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK). Pre-treatment of THP-1 cells with kinase inhibitors reduced PM-induced pro-inflammatory mediator expression. The pro-inflammatory response was also reduced by pre-treatment 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 pre-treatment 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 are a potential model for the development of biologically relevant metrics of long-term spatial variation in exposure for study of chronic disease.