| First Author | Riehl TE | Year | 2004 |
| Journal | Am J Physiol Gastrointest Liver Physiol | Volume | 286 |
| Issue | 1 | Pages | G166-73 |
| PubMed ID | 14525729 | Mgi Jnum | J:87602 |
| Mgi Id | MGI:3027306 | Doi | 10.1152/ajpgi.00537.2002 |
| Citation | Riehl TE, et al. (2004) TNFR1 mediates the radioprotective effects of lipopolysaccharide in the mouse intestine. Am J Physiol Gastrointest Liver Physiol 286(1):G166-73 |
| abstractText | LPS is radioprotective in the mouse small intestine through a mechanism that includes the synthesis of cyclooxygenase-2 (COX-2) and PGE2. The goal of this study was to identify the intermediate steps in this process. We used wild-type (WT) C57BL/6 mice and knockouts for tumor necrosis factor receptors 1 and 2 (TNFR1-/-, TNFR2-/-) and recombination-activating gene 1-/- mice. Mice were given parenteral LPS and then subjected to 12 Gy total body gamma irradiation. The number of surviving intestinal crypts was assessed 3.5 days after irradiation using a clonogenic assay. Crypt cell apoptosis was assessed by histology. Parenteral administration of LPS induced COX-2 expression, PGE2 production, and radioprotection in WT and TNFR2-/- mice but not in TNFR1-/- mice. TNFR1-/- mice were radioprotected by administration of exogenous 16,16-dimethyl PGE2. Immunohistochemical studies localized TNFR1 and COX-2 expression to subeptihelial fibroblasts and villus epithelial cells. Radiation-induced apoptosis was reduced by pretreatment with LPS in WT and TNFR2-/- mice but not in TNFR1-/- mice. In the absence of LPS, crypt survival was elevated in TNFR1-/- when compared with WT mice. These findings demonstrate that TNFR1 function is required for LPS-induced radioprotection in C57BL/6 mice and define an essential role for TNFR1 function in the induction of COX-2 expression and PGE2 production in this process. The immunolocalization of TNFR1 and COX-2 expression to subepithelial fibroblasts following LPS administration suggests that this cell type plays an intermediate role in LPS-induced radioprotection in the intestine. |
