Protein Kinase D2 Protects against Acute Colitis Induced by Dextran Sulfate Sodium in Mice

摘要

Inflammatory bowel disease is characterized by dysregulation of the mucosal immune system resulting from impaired intestinal epithelial barrier function. Protein kinase D2 has been implicated in the regulation of immune responses. The present study was to define PKD2 might affect murine colitis. Colitis was induced in wild-type mice (PKD2(WT/WT)) and PKD2 catalytic activity deficient mice (PKD2(SSAA/SSAA)) with dextran sulfate sodium. PKD2(SSAA)-knockin mice displayed catalytic activity deficiency and increased susceptibility to DSS-induced colitis with enhanced weight loss, colonic inflammation compared with PKD2(WT/WT) mice. Furthermore, crucial inflammatory cytokines mRNA levels in PKD2(SSAA)-knockin mice were higher than controls accompanied with down-regulation of ZO-1, MUC2 and intestinal barrier dysfunction. However, there were no differences in the proliferation or apoptosis of intestinal epithelial cells in PKD2(SSAA)-knockin mice compared with wild-type controls. In addition, PKD2 expression was repressed in patients with IBD compared with healthy controls. These studies suggested that activation of PKD2 in the colonic epithelium microenvironment may contribute to protect against DSS-induced colitis through regulation of intestinal mucosal immunity and barrier function.