Diesel exhaust particulate associated chemicals attenuate expression of CXCL10 in human primary bronchial epithelial cells

Air pollution affects a large proportion of the population particularly in urban areas, with diesel particulates recognised as particular causes for concern in respiratory conditions such as asthma. In this study we examined the response of human primary airway epithelial cells to diesel particulate chemical extracts (DE) and characterised gene expression alterations using RNA-SEQ. Using the antagonist CH223191, DE induced CYP1A1 and attenuation of CXCL10 among other genes were observed to be aryl hydrocarbon receptor dependent. Basal and toll like receptor dependent protein levels for CXCL10 were markedly reduced. Investigation of similar regulation in plasmacytoid dendritic GEN2.2 cells did not show DE dependent regulation of CXCL10. Instillation of DE into mice to recapitulate airway epithelial exposure to chemical extracts in an in vivo setting failed to demonstrate a reduction in CXCL10. There was however an increase in the Th2 type epithelial cell derived inflammatory mediators TSLP and SERPINB2. We also observed an increased macrophages and a decrease in the proportion of lymphocytes in bronchoalveolar lavage fluid. CXCL10 can play a role in allergic airway disease through recruitment of Th1 type CD4 + T-cells, which can act to counterbalance Th2 type allergic responses. Modulation of such chemokines within the airway epithelium may represent a mechanism through which pollutant material can modify respiratory conditions such as allergic asthma.