Murine P-glycoprotein deficiency alters intestinal injury repair and blunts lipopolysaccharide-induced radioprotection

Academic Article

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. © 2012 by Radiation Research Society.
  • Published In

  • Radiation Research  Journal
  • Digital Object Identifier (doi)

    Author List

  • Staley EM; Yarbrough VR; Schoeb TR; Daft JG; Tanner SM; Steverson D; Lorenz RG
  • Start Page

  • 207
  • End Page

  • 216
  • Volume

  • 178
  • Issue

  • 3