【医学课件】 Adverse Effects of Arsenic on the Immune Response of the Lungs to Pseudomonas Infection.ppt

* * * * * * * * * * * * * * * * * * Adverse Effects of Arsenic on the Immune Response of the Lungs to Pseudomonas Infection Bruce A. Stanton, Ph.D. Director, Dartmouth Superfund Research Program October 31, 2016 Outline Sources of arsenic exposure Arsenic and human health Innate immune function of the lung in response to Pseudomonas infection Arsenic suppresses the innate immune function of lung epithelial cells and professional immune cells (macrophages) ATSDR list of substances that pose the most threat to public health /spl/ Google images Sources of arsenic exposure Google images and EHP Arsenic exposure in the US Total arsenic consumption in the US from water, rice and rice based products is 10-25 ppb/day per person. This is equal to drinking 1 to 2.5 liters of water/day containing 10 ppb of arsenic (EPA limit). Arsenic in well water. ~3 million drink well water 10 ppb Arsenic and human disease Google images Nayak, Kim, et al. Toxicol. Sci. 2007 Arsenic enhances viral and bacterial infections in zebrafish Pseudomonas aeruginosa (Pa) Pa is a ubiquitous, opportunistic pathogen that is found in burn wounds, UTIs, and lungs in patients with COPD and CF Pa develops drug resistant biofilms Innate immunity in the lung Antimicrobial peptides Pathogens (bacteria, viruses) Mucus Macrophages Neutrophils Epithelial cells Antigen presentation I IL-8, CXCL1, CXCL2 IL-1b Arsenic reduces chloride secretion by lung epithelial cells Goodale, Barnaby and Stanton, 2016 CFTR Chloride Secretion Arsenic increases the ubiquitination and proteasomal degradation of CFTR Bomberger and Stanton, J. Biol. Chem. 2012 iArsenic reduces Pa stimulated IL-8 and CXCL1 secretion by lung epithelial cells Notch, Goodale, Stanton, PLoS One, 2015 iArsenic reduces Pa stimulated IL-1β secretion by human macrophages Notch and Stanton, unpublished, 2016 I MMA reduces Pa stimulated IL-1β secretion by macrophages Notch and Stanton, unpublished, 2016 I DMA has no effect on Pa stimu