Lipopolysaccharide is radioprotective in the mouse intestine through a prostaglandin-mediated mechanism

被引:115
作者
Riehl, T
Cohn, S
Tessner, T
Schloemann, S
Stenson, WF
机构
[1] Washington Univ, Sch Med, Div Gastroenterol, St Louis, MO 63110 USA
[2] Univ Virginia, Div Gastroenterol, Charlottesville, VA USA
关键词
D O I
10.1016/S0016-5085(00)70363-5
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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.
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页码:1106 / 1116
页数:11
相关论文
共 45 条
[1]   ORIGIN, DIFFERENTIATION AND RENEWAL OF 4 MAIN EPITHELIAL-CELL TYPES IN MOUSE SMALL INTESTINE .5. UNITARIAN THEORY OF ORIGIN OF 4 EPITHELIAL-CELL TYPES [J].
CHENG, H ;
LEBLOND, CP .
AMERICAN JOURNAL OF ANATOMY, 1974, 141 (04) :537-&
[2]  
COHN SM, 1984, J BIOL CHEM, V259, P2456
[3]   USE OF TRANSGENIC MICE TO MAP CIS-ACTING ELEMENTS IN THE INTESTINAL FATTY-ACID BINDING-PROTEIN GENE (FABPI) THAT CONTROL ITS CELL LINEAGE-SPECIFIC AND REGIONAL PATTERNS OF EXPRESSION ALONG THE DUODENAL COLONIC AND CRYPT VILLUS AXES OF THE GUT EPITHELIUM [J].
COHN, SM ;
SIMON, TC ;
ROTH, KA ;
BIRKENMEIER, EH ;
GORDON, JI .
JOURNAL OF CELL BIOLOGY, 1992, 119 (01) :27-44
[4]   Crypt stem cell survival in the mouse intestinal epithelium is regulated by prostaglandins synthesized through cyclooxygenase-1 [J].
Cohn, SM ;
Schloemann, S ;
Tessner, T ;
Seibert, K ;
Stenson, WF .
JOURNAL OF CLINICAL INVESTIGATION, 1997, 99 (06) :1367-1379
[5]  
COLEMAN RA, 1994, PHARMACOL REV, V46, P205
[6]   UP-REGULATION OF CYCLOOXYGENASE-2 GENE-EXPRESSION IN HUMAN COLORECTAL ADENOMAS AND ADENOCARCINOMAS [J].
EBERHART, CE ;
COFFEY, RJ ;
RADHIKA, A ;
GIARDIELLO, FM ;
FERRENBACH, S ;
DUBOIS, RN .
GASTROENTEROLOGY, 1994, 107 (04) :1183-1188
[7]   Role of intestinal epithelial cells in the host secretory response to infection by invasive bacteria - Bacterial entry induces epithelial prostaglandin H synthase-2 expression and prostaglandin E-2 and F-2 alpha production [J].
Eckmann, L ;
Stenson, WF ;
Savidge, TC ;
Lowe, DC ;
Barrett, KE ;
Fierer, J ;
Smith, JR ;
Kagnoff, MF .
JOURNAL OF CLINICAL INVESTIGATION, 1997, 100 (02) :296-309
[8]   DIFFERENTIATION AND SELF-RENEWAL IN THE MOUSE GASTROINTESTINAL EPITHELIUM [J].
GORDON, JI ;
HERMISTON, ML .
CURRENT OPINION IN CELL BIOLOGY, 1994, 6 (06) :795-803
[9]   16,16-DIMETHYL PROSTAGLANDIN-E-2 INDUCES RADIOPROTECTION IN MURINE INTESTINAL AND HEMATOPOIETIC STEM-CELLS [J].
HANSON, WR ;
AINSWORTH, EJ .
RADIATION RESEARCH, 1985, 103 (02) :196-203
[10]   COMPARISON OF INVIVO MURINE INTESTINAL RADIATION PROTECTION BY E-PROSTAGLANDINS [J].
HANSON, WR ;
DELAURENTIIS, K .
PROSTAGLANDINS, 1987, 33 :93-104