4. Discussion
The intact function of intestinal barrier is mainly determined by TJs, which function as a physical barrier between the lumen and the internal milieu. The ‘‘leaky gut”, resulting from the decreased intestinal barrier function, played a pivotal role in the pathogenesis of multiple kinds of diseases including endotoxemia by allowing increased flux of noxious antigens into the internal milieu, leading to unremitting inflammatory responses. The increased level of LPS in the plasma, commonly seen in the context of endotoxemia, has been reported to induce intestinal barrier injury through multiple mechanisms, including decreasing expression of TJ proteins and altering localization of TJs via NF-kB signaling. Upon activation, NF-kB p65 binds to the MLCK promoter region and increases the expression of MLCK mRNA [31,32]. The increased phosphorylation of MLC2 mediated by MLCK leads to contraction of actin-myosin filaments, resulting in altered localization of TJ proteins and consequently, the functional opening of TJs [33,34]. These studies imply the existence of a vicious cycle in the intestinal epithelium consisting of the inflammatory response and the injured intestinal barrier function in the context of endotoxemia. Thus, it remains a promising method for seeking potential therapeutic reagents for endotoxemia by verifying novel regents that may have protective effect on the intestinal barrier function.
