Enterocyte-derived TAK1 signaling prevents epithelium apoptosis and the development of ileitis and colitis.

Ileitis and Colitis of Epithelium Apoptosis and the Development Enterocyte-Derived TAK1 Signaling Prevents

Intestinal Epithelial-Derived TAK1 Signaling Is Essential for Cytoprotection against Chemical-Induced Colitis

BACKGROUND We have previously reported that intestinal epithelium-specific TAK1 deleted mice exhibit severe inflammation and mortality at postnatal day 1 due to TNF-induced epithelial cell death. Although deletion of TNF receptor 1 (TNFR1) can largely rescue those neonatal phenotypes, mice harboring double deletion of TNF receptor 1 (TNFR1) and intestinal epithelium-specific deletion of TAK1 (T...

TGF-beta-activated kinase 1 signaling maintains intestinal integrity by preventing accumulation of reactive oxygen species in the intestinal epithelium.

The intestinal epithelium is constantly exposed to inducers of reactive oxygen species (ROS), such as commensal microorganisms. Levels of ROS are normally maintained at nontoxic levels, but dysregulation of ROS is involved in intestinal inflammatory diseases. In this article, we report that TGF-β-activated kinase 1 (TAK1) is a key regulator of ROS in the intestinal epithelium. tak1 gene deletio...

Infliximab and Etanercept Are Equally Effective in Reducing Enterocyte APOPTOSIS in Experimental Colitis

Loss of epithelial barrier integrity is considered an early step in the pathogenesis of Crohn's disease (CD), and the rate of enterocyte apoptosis is one of the determinants of the intestinal barrier function. Tumor necrosis factor-alpha (TNF-alpha), one of the major proinflammatory mediators in CD, is one of the extrinsic signals which initiate apoptosis of enterocytes. The aim of this study w...

TAK1 is indispensable for development of T cells and prevention of colitis by the generation of regulatory T cells.

Transforming growth factor (TGF)-beta-activating kinase 1 (TAK1) is critical for Toll-like receptor- and tumor necrosis factor-mediated cellular responses. In B cells, TAK1 is essential for the activation of mitogen-activated protein kinases (MAPKs), but not nuclear factor-kappaB (NF-kappaB), in antigen receptor signaling. In this study, we generate T cell-specific TAK1-deficient (Lck(Cre/(+))T...