| First Author | Mizushima T | Year | 2013 |
| Journal | Am J Pathol | Volume | 183 |
| Issue | 6 | Pages | 1936-44 |
| PubMed ID | 24266926 | Mgi Jnum | J:207935 |
| Mgi Id | MGI:5559959 | Doi | 10.1016/j.ajpath.2013.08.012 |
| Citation | Mizushima T, et al. (2013) Inhibition of epithelial cell death by Bcl-2 improved chronic colitis in IL-10 KO mice. Am J Pathol 183(6):1936-44 |
| abstractText | IL-10-deficient mice spontaneously develop intestinal inflammation, which has many similarities to Crohn's disease. Several reports suggest that epithelial cell death may increase the severity of colitis; however, decisive evidence is lacking. In the present report, we addressed whether and how epithelial cell death plays a role in the development of chronic colitis. We first examined the morphological characteristics of intestines of IL-10-deficient mice and found two forms of epithelial cell death (typical apoptosis and necrosis-like cell death) in colitis. To elucidate the pathological roles of epithelial cell death, we crossbred IL-10-deficient knockout mice with Bcl-2 transgenic mice, in which the anti-apoptosis protein Bcl-2 was overexpressed in intestinal epithelial cells, but not in immune cells. Epithelial cell-specific Bcl-2 protected IL-10 deficiency-induced colitis and markedly reduced their symptoms. Interestingly, morphological analysis revealed that Bcl-2 suppressed apoptosis and necrosis-like cell death, and better maintained mucosal barrier in IL-10-deficient mice. From the immunological aspect, Bcl-2 did not alter the activation of T-helper cell 1 but inhibited the growth of T-helper cell 17, suggesting that mucosal integrity may control the immune responses. These results provide genetic evidence demonstrating that epithelial cell death is crucial for the development of chronic colitis. |
