期刊
ARCHIVES OF TOXICOLOGY
卷 89, 期 4, 页码 555-564出版社
SPRINGER HEIDELBERG
DOI: 10.1007/s00204-014-1271-1
关键词
Arsenic; Caco-2; Cytokines; Inflammation; Intestinal epithelium; Peripheral blood mononuclear cells
类别
资金
- Spanish Ministry of Science and Innovation [AGL2009-10100]
- Ministry of Economy and Competitiveness [AGL2012-33461]
- Spanish Ministry of Science and Education
Chronic exposure to inorganic arsenic (As) is associated with type 2 diabetes, cardiovascular diseases and cancer. Ingested inorganic As is transformed within the gastrointestinal tract and can give rise to more toxic species such as monomethylarsonous acid [MMA(III)] and dimethylarsinous acid [DMA(III)]. Thus, the intestinal epithelium comes into contact with toxic arsenical species, and the effects of such exposure upon epithelial function are not clear. The present study has evaluated the effect of 1 A mu M arsenite [As(III)], 0.1 A mu M MMA(III) and 1 A mu M DMA(III) upon the release of cytokines [interleukin-6 (IL6), IL8, tumor necrosis factor alpha (TNF alpha)], using a compartmentalized co-culture model with differentiated Caco-2 cells in the apical compartment and peripheral blood mononuclear cells in the basolateral compartment. In addition, the combined effect of arsenical species and lipopolysaccharide (LPS), both added into the apical compartment, has been analyzed. The results indicate that exposure to the arsenical forms induces a proinflammatory response. An increase in cytokine secretion into the basolateral compartment was observed, particularly as regards TNF alpha (up to 1,600 %). The cytokine levels on the apical side also increased, though to a lesser extent. As/LPS co-exposure significantly affected the proinflammatory response as compared to treatment with As alone. Treatment with DMA(III) and As/LPS co-exposure increased the permeability of the intestinal monolayer. In addition, As/LPS treatments enhanced As(III) and MMA(III) transport through the intestinal monolayer.
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