科研之友
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摘要
Interleukin-1 beta (IL-1 beta) has been shown to play an essential role in mediating intestinal inflammation of Crohn%26apos;s disease and other inflammatory conditions of the gut. Previous studies from our laboratory have shown that IL-1 beta causes an increase in intestinal tight-junction permeability in Caco-2 monolayers in vitro. However, the IL-1 beta effect on the intestinal epithelial barrier in vivo remains unclear. Aims: the major aims of this study were to examine the effect of IL-1 beta on mouse intestinal epithelial barrier in vivo and to delineate the mechanisms involved using an in vivo model system consisting of a recycling perfusion of mouse small intestine. Intraperitonial injection of IL-1 beta at varying doses (0-10 mu g) caused a concentration-dependent increase in mouse intestinal permeability to the paracellular marker dextran (10 KD), and the maximal increase in dextran flux occurred at IL-1 beta dose of 5 mg. IL-1 beta treatment caused an increase in myosin light-chain kinase (MLCK) mRNA and protein expression in the small intestinal tissue starting at 24 h, which continued up to 72 h. Additionally, IL-1 beta did not cause an increase in intestinal permeability in MLCK-deficient mice (C57BL/6 MLCK-/-). MLCK inhibitor ML-7 (2 mg/kg body weight) also inhibited the IL-1 beta-induced increase in small intestinal permeability. The IL-1 beta-induced increase in mouse intestinal permeability was associated with an increase in NF-kappa B activation. The intestinal tissue-specific silencing of NF-kappa B p65 inhibited the IL-1 beta-induced increase in intestinal permeability and increase in MLCK expression. These data show for the first time that IL-1 beta causes an increase in mouse intestinal permeability in vivo. These data suggested that the mechanism of IL-1 beta-induced increase in mouse intestinal permeability in vivo involved NF-kappa B p65-induced activation of the mouse enterocyte MLCK gene.
- 出版日期2012-10
- 单位西北大学
