Monomethylarsonous Acid (MMAIII) Has an Adverse Effect on the Innate Immune Response of Human Bronchial Epithelial Cells to Pseudomonas aeruginosa

Arsenic is the number one contaminant of concern with regard to human health according to the World Health Organization. Epidemiological studies on Asian and South American populations have linked arsenic exposure with an increased incidence of lung disease, including pneumonia, and chronic obstructive pulmonary disease, both of which are associated with bacterial infection. However, little is known about the effects of low dose arsenic exposure, or the contributions of organic arsenic to the innate immune response to bacterial infection. This study examined the effects on Pseudomonas aeruginosa ( P . aeruginosa) induced cytokine secretion by human bronchial epithelial cells (HBEC) by inorganic sodium arsenite (iAs III ) and two major metabolites, monomethylarsonous acid (MMA III ) and dimethylarsenic acid (DMA V ), at concentrations relevant to the U.S. population. Neither iAs III nor DMA V altered P . aeruginosa induced cytokine secretion. By contrast, MMA III increased P . aeruginosa induced secretion of IL-8, IL-6 and CXCL2. A combination of iAs III , MMA III and DMA V (10 pbb total) reduced IL-8 and CXCL1 secretion. These data demonstrate for the first time that exposure to MMA III alone, and a combination of iAs III , MMA III and DMA V at levels relevant to the U.S. may have negative effects on the innate immune response of human bronchial epithelial cells to P . aeruginosa .