title: Lipopolysaccharide is radioprotective in the mouse intestine through a prostaglandin-mediated mechanism.
abstract: OBJECTIVE
  The bone marrow and the intestine are the major sites of radiation-induced injury. The cellular response to radiation injury in the intestine or bone marrow can be modulated by agents given before irradiation. Lipopolysaccharide is known to be radioprotective in the bone marrow, but its effect on the intestine is not known. We sought to determine if lipopolysaccharide is radioprotective in the intestine and, if so, to determine the mechanism of its radioprotective effects.
  
  
  METHODS
  Mice were treated with parenteral lipopolysaccharide or vehicle and then irradiated (14 Gy total body irradiation in a cesium irradiator). The number of surviving intestinal crypts was assessed 3.5 days after irradiation using a clonogenic assay.
  
  
  RESULTS
  Parenteral administration of lipopolysaccharide 2-24 hours before irradiation resulted in a 2-fold increase in the number of surviving crypts 3.5 days after irradiation. The radioprotective effects of lipopolysaccharide could be eliminated by coadministration of a selective inhibitor of cyclooxygenase 2. Lipopolysaccharide was radioprotective in wild-type mice but not in mice with a disrupted cyclooxygenase 2. Parenteral administration of lipopolysaccharide resulted in increased production of prostaglandins in the intestine and in the induction of cyclooxygenase 2 expression in subepithelial fibroblasts and in villous, but not crypt, epithelial cells.
  
  
  CONCLUSIONS
  Lipopolysaccharide is radioprotective in the mouse intestine through a prostaglandin-dependent pathway.
authors.affiliation: Division of Gastroenterology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: T
authors.initials: T
authors.lastname: Riehl
authors.forename: S
authors.initials: S
authors.lastname: Cohn
authors.forename: T
authors.initials: T
authors.lastname: Tessner
authors.forename: S
authors.initials: S
authors.lastname: Schloemann
authors.forename: W F
authors.initials: WF
authors.lastname: Stenson
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001831:Body Temperature; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology / Q000528:radiation effects; D005260:Female; D005838:Genotype; D007213:Indomethacin / Q000494:pharmacology; D007421:Intestine, Small / Q000201:enzymology* / Q000473:pathology; D007527:Isoenzymes / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009578:Nitrobenzenes / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D011833:Radiation Injuries, Experimental / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D009578:Nitrobenzenes; D011837:Radiation-Protective Agents; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496512:Ptgs1 protein, mouse; D015232:Dinoprostone; D007213:Indomethacin