Inhibition of β-defensin gene expression in airway epithelial cells by low doses of residual oil fly ash is mediated by vanadium

Poor ambient air quality is associated with increased morbidity and mortality, including respiratory infections. However, its effects on various host-defense mechanisms are poorly understood. This study utilized an in vitro model to study the effect of particulate matter (PM2.5) on one antimicrobial mechanism of host defense in the airway, beta-defensin-2 and its bovine homologue, tracheal antimicrobial peptide (TAP) induction in response to lipopolysaccharide (LPS) and IL-1 beta. Our model utilized cultured primary bovine tracheal epithelial (BTE) cells and the human alveolar type II epithelial cell line, A549, treated with 0-20 mu g/cm(2) residual oil fly ash (ROFA) for 6 It. The cells were then washed and stimulated for 18 h with 100 ng/ml LPS or for 6 h with 100 ng/mI IL-1 beta. ROFA inhibited the LPS-induced increase in TAP mRNA and protein without inducing significant: cytotoxicity. As little as 2.5 mu g/cm(2) of ROFA inhibited LPS-induced TAP gene expression by 30%. The inhibitory activity was associated with the soluble fraction and not the washed particle. The activity in the leachate was attributed to vanadium, but not nickel or iron. SiO2 and TiO2 were utilized as controls and did not inhibit LPS induction of TAP gene expression in BTE. ROFA also inhibited the increase of IL-I beta-induced human beta-defensin-2, a homologue of TAP, in A549 cells. The results show that ROFA, V2O5, and VOSO4 inhibit the ability of airway epithelial cells to respond to inflammatory stimuli at low, physiologically relevant doses and suggest that exposure to these agents could result in an impairment of defense against airborne pathogens.