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1 September 2012 Murine P-glycoprotein Deficiency Alters Intestinal Injury Repair and Blunts Lipopolysaccharide-Induced Radioprotection
Elizabeth M. Staley, Vanisha R. Yarbrough, Trenton R. Schoeb, Joseph G. Daft, Scott M. Tanner, Dennis Steverson Jr., Robin G. Lorenz
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Abstract

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 (PGE2) 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-1α, 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-1α in radioprotection, and demonstrating that P-gp deficiency interferes with IL-1α gene expression in response to systemic exposure to LPS.

Elizabeth M. Staley, Vanisha R. Yarbrough, Trenton R. Schoeb, Joseph G. Daft, Scott M. Tanner, Dennis Steverson Jr., and Robin G. Lorenz "Murine P-glycoprotein Deficiency Alters Intestinal Injury Repair and Blunts Lipopolysaccharide-Induced Radioprotection," Radiation Research 178(3), 207-216, (1 September 2012). https://doi.org/10.1667/RR2835.1
Received: 25 October 2011; Accepted: 1 January 2012; Published: 1 September 2012
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