BACKGROUND
Intestinal alkaline phosphatase (IAP) plays a pivotal role in maintaining gut health and well-being. Oral supplementation with IAP in mice improves gut barrier function and prevents luminal proinflammatory factors from gaining access to the circulation. In this study, we sought to explore the relationship between IAP and tight junction protein (TJP) expression and function.
STUDY DESIGN
The effect of IAP deletion on TJP levels was studied in mouse embryonic fibroblasts (MEFs) generated from IAP-knockout and wild type mice. Regulation of TJPs by IAP was assayed in the human colon cancer Caco-2 and T84 cells by overexpressing the human IAP gene. Tight junction protein levels and localization were measured by using RT q-PCR and antibodies targeting the specific TJPs. Finally, the effect of IAP on inflammation-induced intestinal permeability was measured by in vitro trans-well epithelial electrical resistance (TEER).
RESULTS
Intestinal alkaline phosphatase gene deletion in MEFs resulted in significantly lower levels of ZO-1, ZO-2, and Occludin compared with levels in wild-type control cells; IAP over-expression in Caco-2 and T84 cells resulted in approximate 2-fold increases in the mRNA levels of ZO-1 and ZO-2. The IAP treatment ameliorated lipopolysaccharide-induced increased permeability in the Caco-2 trans-well system. Furthermore, IAP treatment preserved the localization of the ZO-1 and Occludin proteins during inflammation and was also associated with improved epithelial barrier function.
CONCLUSIONS
Intestinal alkaline phosphatase is a major regulator of gut mucosal permeability and appears to work at least partly through improving TJP levels and localization. These data provide a strong foundation to develop IAP as a novel therapy to maintain gut barrier function.
The emetic responses induced by staphylococcal enterotoxin A (SEA), SEB, SEC2, SED, SEE, SEG, SEH, and SEI in the house musk shrew (Suncus murinus) were investigated. SEA, SEE, and SEI showed higher emetic activity in the house musk shrew than the other SEs. SEB, SEC2, SED, SEG, and SEH also induced emetic responses in this animal model but relatively high doses were required. The house musk shrew appears to be a valuable model for studying the mechanisms of emetic reactions caused by SEs.
Preoperative EEN reduced the risk of postoperative IASCs after operation for ECFs in CD. In addition, age at operation may be another factor of influence.
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