Abstract
Osmotic stress plays a crucial role in the pathogenesis of many gastrointestinal diseases. Lactobacillus casei and epidermal growth factor (EGF) effects on the osmotic stress-induced epithelial junctional disruption and barrier dysfunction were investigated. Caco-2 cell monolayers were exposed to osmotic stress in the presence or absence of L. casei or EGF, and the barrier function was evaluated by measuring inulin permeability. Tight junction (TJ) and adherens junction integrity were assessed by immunofluorescence confocal microscopy. The role of signaling molecules in the L. casei and EGF effects was determined by using selective inhibitors. Data show that pretreatment of cell monolayers with L. casei or EGF attenuates osmotic stress-induced TJ and adherens junction disruption and barrier dysfunction. EGF also blocked osmotic stress-induced actin cytoskeleton remodeling. U0126 (MEK1/2 inhibitor), the MAP kinase inhibitor, blocked EGF-mediated epithelial protection from osmotic stress. In contrast, the L. casei-mediated epithelial protection from osmotic stress was unaffected by U0126, AG1478 (EGFR tyrosine kinase inhibitor), SP600125 (JNK1/2 inhibitor), or SB202190 (P38 MAP kinase inhibitor). On the other hand, Ro-32-0432 (PKC inhibitor) blocked the L. casei-mediated prevention of osmotic stress-induced TJ disruption and barrier dysfunction. The combination of EGF and L. casei is more potent in protecting the barrier function from osmotic stress. These findings suggest that L. casei and EGF ameliorate osmotic stress-induced disruption of apical junctional complexes and barrier dysfunction in the intestinal epithelium by distinct signaling mechanisms.
Highlights
Intestinal mucosal barrier function is mainly conferred by the epithelial tight junction (TJ) that prevents diffusion of allergens, toxins, and pathogens across the epithelium and subsequently into the systemic circulation [1,2]
Disruption of epithelial tight junction is anwith essential passage for water to diarrhea is a common type of diarrhea associated various
Disruption of epithelial tight junction is an essential passage for water to flow into tive strategy in preventing osmotic diarrhea and leakage of toxins across the epithelium
Summary
Intestinal mucosal barrier function is mainly conferred by the epithelial tight junction (TJ) that prevents diffusion of allergens, toxins, and pathogens across the epithelium and subsequently into the systemic circulation [1,2]. Mucosal protective factors in the gut may protect the epithelium from osmotic stress. In previous in vitro and ex vivo studies, we have observed that osmotic stress disrupts the intestinal epithelial TJ and causes barrier dysfunction [32,33]. 393, one of the first identified strains of the L. casei group, exhibits distinct mucosal adhesiveness, the property essential for its beneficial function in the GI tract [44]. L. casei ATCC 393 strain reduced tumor volume in an experimental colon cancer model [45] and alleviated enterotoxigenic E. coli-induced intestinal barrier dysfunction [46]. The effects of L. casei or EGF on osmotic stress-induced epithelial injury are unknown. In this study, we investigated the effect of L. casei ATCC 393 and EGF on the osmotic stress-induced barrier dysfunction and disruption of apical junctional complexes in the intestinal epithelium
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