Characterization of in vitro effects of microcystin-LR on intestinal epithelial cells.

The intestinal epithelium is a single-cell layer that provides an important barrier against natural toxins. Microcystin-LR (MC-LR), a cyclic heptapeptide, is one of the best known toxins able to alter the functions of intestine. This study evaluated the toxic effects and the possible mechanisms of MC-LR on barrier function of the intestinal epithelial cells. Intestinal epithelial cells (IEC-6) were exposed to 0, 6.25, 12.5, 25 and 50 μM MC-LR. Cell viability significantly decreased, while the ratio of apoptotic cells increased after exposure to 12.5μM and higer concentration of MC-LR. As expected, the integrity of a polarized IEC-6 monolayer was affected by MC-LR exposure, as demonstrated by a decrease in the transepithelial electrical resistance (TEER) values, becoming most pronounced at 50μM, 24 h. No effects were detected on the protein expression levels of the tight junction protein claudin at 50μM. However, the expression of occludin and zonula occludens-1 (ZO-1) declined. Furthermore, MC-LR can immigrate into IEC-6 cells. The activity of protein phosphatases 2A (PP2A) decreased from the concentration of 12.5 μM, showing a dose-dependent decline. These results provide new information that strengthens the concept that the intestinal epithelium is important targets for toxic effects of water contaminants like MC-LR. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1539-1547, 2017.