Prostaglandins (PGs) are important mediators of epithelial integrity and function in the gastrointestinal tract. Relatively little is known, however, about the mechanism by which PGs affect stem cells in the intestine during normal epithelial turnover, or during wound repair. PGs are synthesized from arachidonate by either of two cyclooxygenases, cyclooxygenase-1 (Cox-1) or cyclooxygenase-2 (Cox-2), which are present in a wide variety of mamalian cells. Cox-1 is thought to be a constitutively expressed enzyme, and the expression of Cox-2 is inducible by cytokines or other stimuli in a variety of cell types. We investigated the role of PGs in mouse intestinal stem cell survival and proliferation following radiation injury. The number of surviving crypt stem cells was determined 3.5 d after irradiation by the microcolony assay. Radiation injury induced a dose-dependent decrease in the number of surviving crypts. Indomethacin, an inhibitor of Cox-1 and Cox-2, further reduced the number of surviving crypts in irradiated mice. The indomethacin dose response for inhibition of PGE2 production and reduction of crypt survival were similar. DimethylPGE2 reversed the indomethacin-induced decrease in crypt survival. Selective Cox-2 inhibitors had no effect on crypt survival. PGE2, Cox-1 mRNA, and Cox-1 protein levels all increase in the 3 d after irradiation. Immunohistochemistry for Cox-1 demonstrated localization in epithelial cells of the crypt in the unirradiated mouse, and in the regenerating crypt epithelium in the irradiated mouse. We conclude that radiation injury results in increased Cox-1 levels in crypt stem cells and their progeny, and that PGE2 produced through Cox-1 promotes crypt stem cell survival and proliferation.
S M Cohn, S Schloemann, T Tessner, K Seibert, W F Stenson
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Molecular and Cellular Endocrinology | 2002 |
Potential role of the membrane in the development of intestinal cellular damage after whole-body gamma irradiation of the rat
F Lebrun, M Benderitter, A Berroud, P Voisin, NM Griffiths |
Canadian Journal of Physiology and Pharmacology | 2002 |
Impact of Helicobacter pylori and nonsteroidal anti-inflammatory drugs on gastric ulcerogenesis in experimental animals and in humans
T Pawlik, PC Konturek, JW Konturek, SJ Konturek, T Brzozowski, M Cześnikiewicz, M Plonka, W Bielanski, H Areny |
European Journal of Pharmacology | 2002 |
A novel human fibroblast growth factor treats experimental intestinal inflammation
M Jeffers, WF McDonald, RA Chillakuru, M Yang, H Nakase, LL Deegler, ED Sylander, B Rittman, A Bendele, RB Sartor, HS Lichenstein |
Gastroenterology | 2002 |
Rapid development of colitis in NSAID-treated IL-10–deficient mice
DJ Berg, J Zhang, JV Weinstock, HF Ismail, KA Earle, H Alila, R Pamukcu, S Moore, RG Lynch |
Gastroenterology | 2002 |
Role of human heme oxygenase-1 in attenuating TNF-?-mediated inflammation injury in endothelial cells
T Kushida, GL Volti, S Quan, A Goodman, NG Abraham |
Journal of Cellular Biochemistry | 2002 |
Prostaglandins are required for CREB activation and cellular proliferation during liver regeneration
DA Rudnick, DH Perlmutter, LJ Muglia |
Proceedings of the National Academy of Sciences | 2001 |
Molecular mechanisms contributing to necrotizing enterocolitis
DH Chung, RT Ethridge, S Kim, S Owens-Stovall, A Hernandez, DR Kelly, BM Evers |
Annals of Surgery | 2001 |
Regulation of cyclo-oxygenase-2
E Stack, RN DuBois |
Best Practice & Research Clinical Gastroenterology | 2001 |
Celecoxib, a selective cyclo-oxygenase-2 inhibitor reduces the severity of experimental colitis induced by dinitrobenzene sulfonic acid in rats
S Cuzzocrea, E Mazzon, I Serraino, L Dugo, T Centorrino, A Ciccolo, L Sautebin, AP Caputi |
European Journal of Pharmacology | 2001 |
Expression of cyclooxygenase-2 protein in colon disease
H Lu, Z Ge, W Liu, X Chen, Y Peng, S Xiao |
Chinese Journal of Digestive Diseases | 2001 |
Molecular Mechanisms Contributing to Necrotizing Enterocolitis
DH Chung, RT Ethridge, S Kim, S Owens-Stovall, A Hernandez, DR Kelly, BM Evers |
Annals of Surgery | 2001 |
CLINICAL IMPLICATIONS OF PROSTAGLANDIN INHIBITION IN THE SMALL BOWEL
CW Houchen |
Gastroenterology Clinics of North America | 2001 |
Differential roles of cyclooxygenase isoforms after kainic acid-induced prostaglandin E2 production and neurodegeneration in cortical and hippocampal cell cultures
EJ Kim, JE Lee, KJ Kwon, SH Lee, CH Moon, EJ Baik |
Brain Research | 2001 |
Inflammation
JA Hunt |
Encyclopedia of Materials Science and Technology | 2001 |
Prostanoid production via COX-2 as a causative mechanism of rodent postoperative ileus
NT Schwarz, JC Kalff, A Türler, BM Engel, SC Watkins, TR Billiar, AJ Bauer |
Gastroenterology | 2001 |
Effects of Nonsteroidal Anti-Inflammatory Drugs on Helicobacter pylori -Infected Gastric Mucosae of Mice: Apoptosis, Cell Proliferation, and Inflammatory Activity
JD Clements, TI Kim, YC Lee, KH Lee, JH Han, CY Chon, YM Moon, JK Kang, IS Park |
Infection and immunity | 2001 |
Impaired mucosal defense to acute colonic injury in mice lacking cyclooxygenase-1 or cyclooxygenase-2
O Morteau, SG Morham, R Sellon, LA Dieleman, R Langenbach, O Smithies, RB Sartor |
Journal of Clinical Investigation | 2000 |
Review article: new insights into the pathogenesis of radiation-induced intestinal dysfunction
Macnaughton |
Alimentary Pharmacology & Therapeutics | 2000 |
Cyclooxygenase-2 and carcinogenesis
SM Prescott, FA Fitzpatrick |
Biochimica et Biophysica Acta (BBA) - Reviews on Cancer | 2000 |
Lipopolysaccharide is radioprotective in the mouse intestine through a prostaglandin-mediated mechanism
T Riehl, S Cohn, T Tessner, S Schloemann, WF Stenson |
Gastroenterology | 2000 |
Myofibroblasts: paracrine cells important in health and disease
DW Powell |
Transactions of the American Clinical and Climatological Association | 2000 |
Eicosanoids and the small intestine
B Mohajer, TY Ma |
Prostaglandins & Other Lipid Mediators | 2000 |
Aspirine, douleurs et inflammation
P Vergne, P Bertin, R Trèves |
La Revue de Médecine Interne | 2000 |
Disruption of cyclooxygenase-1 gene results in an impaired response to radiation injury
CW Houchen, WF Stenson, SM Cohn |
AJP Gastrointestinal and Liver Physiology | 2000 |
Keratinocyte growth factor-2 (FGF-10) promotes healing of experimental small intestinal ulceration in rats
DS Han, F Li, L Holt, K Connolly, M Hubert, R Miceli, Z Okoye, G Santiago, K Windle, E Wong, RB Sartor |
AJP Gastrointestinal and Liver Physiology | 2000 |
The Mom1AKR intestinal tumor resistance region consists of Pla2g2a and a locus distal to D4Mit64
RT Cormier, A Bilger, AJ Lillich, RB Halberg, KH Hong, KA Gould, N Borenstein, ES Lander, WF Dove |
Oncogene | 2000 |
Mode of action of ANG II on ion transport in guinea pig distal colon
Y Hosoda, A Winarto, T Iwanaga, A Kuwahara |
AJP Gastrointestinal and Liver Physiology | 2000 |
Effect of Intrarectal Prostaglandin E 2 Analogue (Enprostil) on Trinitrobenzenesulphonic Acid-Induced Colitis in Rats
Y Onizuka, K Murase, H Furusu, H Isomoto, Y Mizuta, F Takeshima, K Makiyama, S Kohno |
J INT MED RES | 2000 |
Cyclooxygenase-1 and an alternatively spliced mRNA in the rat stomach: effects of aging and ulcers
D Vogiagis, EM Glare, A Misajon, W Brown, PE O'Brien |
AJP Gastrointestinal and Liver Physiology | 2000 |
Low glutathione peroxidase activity in Gpx1 knockout mice protects jejunum crypts from γ-irradiation damage
RS Esworthy, JR Mann, M Sam, FF Chu |
AJP Gastrointestinal and Liver Physiology | 2000 |
Low endogenous prostaglandin E2 predisposes to relapsing inflammation in experimental rat enterocolitis
H M Kandil, R A Argenzio, R B Sartor |
Digestive Diseases and Sciences | 2000 |
Cyclooxygenase expression in intestinal epithelial cells
CW Houchen, WF Stenson |
Current Opinion in Gastroenterology | 1999 |
Cyclooxygenase 2 selective inhibitors: Panacea or flash in the pan?
U Beejay, MM Wolfe |
Gastroenterology | 1999 |
Selective cyclooxygenase-2 inhibitors as non-ulcerogenic anti-inflammatory agents
AS Kalgutkar |
Expert Opinion on Therapeutic Patents | 1999 |
Myofibroblasts. I. Paracrine cells important in health and disease
D Li, SL Friedman |
The American journal of physiology | 1999 |
Myofibroblasts. II. Intestinal subepithelial myofibroblasts
DW Powell, RC Mifflin, JD Valentich, SE Crowe, JI Saada, AB West |
American journal of physiology. Cell physiology | 1999 |
Prostaglandin-induced recovery of barrier function in porcine ileum is triggered by chloride secretion
AT Blikslager, MC Roberts, RA Argenzio |
AJP Gastrointestinal and Liver Physiology | 1999 |
Selective targeting of cyclooxygenase-2 reveals its role in renal medullary interstitial cell survival
CM Hao, M Kömhoff, Y Guan, R Redha, MD Breyer |
American journal of physiology. Renal physiology | 1999 |
Gastrointestinal Pharmacology
DE Freeman |
The Veterinary clinics of North America. Equine practice | 1999 |
Cyclooxygenase-2-dependent arachidonic acid metabolites are essential modulators of the intestinal immune response to dietary antigen
RD Newberry, WF Stenson, RG Lorenz |
Nature Medicine | 1999 |
FGF-2 enhances intestinal stem cell survival and its expression is induced after radiation injury
CW Houchen, RJ George, MA Sturmoski, SM Cohn |
AJP Gastrointestinal and Liver Physiology | 1999 |
Differential expression of interleukin 1 receptor antagonist isoforms in human intestinal epithelial cells
U Böcker, A Damião, L Holt, DS Han, C Jobin, A Panja, L Mayer, RB Sartor |
Gastroenterology | 1998 |
Cyclooxygenase 2 is induced in colonic epithelial cells in inflammatory bowel disease
II Singer, DW Kawka, S Schloemann, T Tessner, T Riehl, WF Stenson |
Gastroenterology | 1998 |
CYCLOOXYGENASES 1 AND 2
JR Vane, YS Bakhle, RM Botting |
Annual Review of Pharmacology and Toxicology | 1998 |
Specific NF-kappaB blockade selectively inhibits tumour necrosis factor-alpha-induced COX-2 but not constitutive COX-1 gene expression in HT-29 cells
JOBIN, MORTEAU, HAN, BALFOUR SARTOR |
Immunology | 1998 |
Prostaglandins prevent decreased epithelial cell proliferation associated with dextran sodium sulfate injury in mice
TG Tessner, SM Cohn, S Schloemann, WF Stenson |
Gastroenterology | 1998 |
Cyclooxygenase in biology and disease
RN Dubois, SB Abramson, L Crofford, RA Gupta, LS Simon, LB Putte, PE Lipsky |
The FASEB Journal | 1998 |
Selective COX-2 Inhibitors
J Vane, J Botting |
1998 | |
Specific NF-kappaB blockade selectively inhibits tumour necrosis factor-alpha-induced COX-2 but not constitutive COX-1 gene expression in HT-29 cells.
Jobin C, Morteau O, Han DS, Balfour Sartor R |
Immunology | 1998 |
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 E2 and F2alpha production
L Eckmann, WF Stenson, TC Savidge, DC Lowe, KE Barrett, J Fierer, JR Smith, MF Kagnoff |
Journal of Clinical Investigation | 1997 |