| First Author | Staley EM | Year | 2012 |
| Journal | Radiat Res | Volume | 178 |
| Issue | 3 | Pages | 207-16 |
| PubMed ID | 22780103 | Mgi Jnum | J:336957 |
| Mgi Id | MGI:6840074 | Doi | 10.1667/rr2835.1 |
| Citation | Staley EM, et al. (2012) Murine P-glycoprotein deficiency alters intestinal injury repair and blunts lipopolysaccharide-induced radioprotection. Radiat Res 178(3):207-16 |
| abstractText | P-glycoprotein (P-gp) has been reported to increase stem cell proliferation and regulate apoptosis. Absence of P-gp results in decreased repair of intestinal epithelial cells after chemical injury. To further explore the mechanisms involved in the effects of P-gp on intestinal injury and repair, we used the well-characterized radiation injury model. In this model, injury repair is mediated by production of prostaglandins (PGE(2)) and lipopolysaccharide (LPS) has been shown to confer radioprotection. B6.mdr1a(-/-) mice and wild-type controls were subjected to 12 Gy total body X-ray irradiation and surviving crypts in the proximal jejunum and distal colon were evaluated 3.5 days after irradiation. B6.mdr1a(-/-) mice exhibited normal baseline stem cell proliferation and COX dependent crypt regeneration after irradiation. However, radiation induced apoptosis was increased and LPS-induced radioprotection was blunted in the C57BL6.mdr1a(-/-) distal colon, compared to B6 wild-type controls. The LPS treatment induced gene expression of the radioprotective cytokine IL-1alpha, in B6 wild-type controls but not in B6.mdr1a(-/-) animals. Lipopolysaccharid-induced radioprotection was absent in IL-1R1(-/-) animals, indicating a role for IL-1alpha in radioprotection, and demonstrating that P-gp deficiency interferes with IL-1alpha gene expression in response to systemic exposure to LPS. |
