BACKGROUND & AIMS: 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.
BACKGROUND & AIMS: 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: Matthew A Ciorba; Christopher L Hallemeier; William F Stenson; Parag J Parikh Journal: Curr Opin Support Palliat Care Date: 2015-06 Impact factor: 2.302
Authors: Sarbjeet Makkar; Terrence E Riehl; Baosheng Chen; Yan Yan; David M Alvarado; Matthew A Ciorba; William F Stenson Journal: Mol Cancer Ther Date: 2019-09-04 Impact factor: 6.261
Authors: Teresa G Tessner; Filipe Muhale; Terrence E Riehl; Shrikant Anant; William F Stenson Journal: J Clin Invest Date: 2004-12 Impact factor: 14.808
Authors: J L Bishop; M E Roberts; J L Beer; M Huang; M K Chehal; X Fan; L A Fouser; H L Ma; J T Bacani; K W Harder Journal: Mucosal Immunol Date: 2013-09-18 Impact factor: 7.313
Authors: Nabendu Murmu; Jesse Jung; Debnath Mukhopadhyay; Courtney W Houchen; Terrence E Riehl; William F Stenson; Aubrey R Morrison; Thiruvengadam Arumugam; Brian K Dieckgraefe; Shrikant Anant Journal: Proc Natl Acad Sci U S A Date: 2004-09-09 Impact factor: 11.205