| First Author | Ishikawa TO | Year | 2011 |
| Journal | Carcinogenesis | Volume | 32 |
| Issue | 3 | Pages | 417-26 |
| PubMed ID | 21156970 | Mgi Jnum | J:169324 |
| Mgi Id | MGI:4940440 | Doi | 10.1093/carcin/bgq268 |
| Citation | Ishikawa TO, et al. (2011) Cox-2 deletion in myeloid and endothelial cells, but not in epithelial cells, exacerbates murine colitis. Carcinogenesis 32(3):417-26 |
| abstractText | Patients with inflammatory bowel diseases are at increased risk for colorectal cancer. Pharmacological inhibition of cyclooxygenase (COX) function exacerbates symptoms in colitis patients. Animal models of colitis using Cox-2-knockout mice and COX inhibitors also indicate that COX-2 has a protective role against colon inflammation. However, because conventional Cox-2 deletion and COX-2 inhibitors eliminate COX-2 function in all cells, it has not been possible to analyze the role(s) of COX-2 in different cell types. Here, we use a Cox-2(flox) conditional knockout mouse to analyze the role of COX-2 expression in distinct cell types in the colon in response to dextran sulfate sodium (DSS)-induced colitis. We generated Cox-2 conditional knockouts in myeloid cells with LysMCre knock-in mice, in endothelial cells with VECadCreERT2 transgenic mice and in epithelial cells with VillinCre transgenic mice. When treated with DSS to induce colitis, both myeloid cell-specific and endothelial cell-specific Cox-2-knockout mice exhibited greater weight loss, increased clinical scores and decreased epithelial cell proliferation after DSS injury when compared with littermate controls. In contrast, epithelial-specific Cox-2 knockouts and control littermates did not differ in response to DSS. These results suggest that COX-2 expression in myeloid cells and endothelial cells, but not epithelial cells, is important for protection of epithelial cells in this murine colitis model. |
