Prostaglandins prevent decreased epithelial cell proliferation associated with dextran sodium sulfate injury in mice.
OBJECTIVE
Although dextran sodium sulfate (DSS)-induced colitis is a commonly used model of colonic injury, the mechanism of this model is not understood. The aim of this study was to determine the contribution of prostaglandins to the mechanism of DSS-induced epithelial injury.


METHODS
Mice were treated with 3% DSS in the drinking water for 5 days followed by water only (recovery). Tissue prostaglandin E2 (PGE2) levels were measured, proliferating cells per cecal crypt were determined by bromodeoxyuridine labeling, and the cellular localization of cyclooxygenase (COX)-1 and COX-2 was determined by immunohistochemistry.


RESULTS
DSS decreased the number of proliferating epithelial cells per crypt by approximately 90% and decreased the height of cecal crypts by 40%. Administration of dimethyl PGE2 with DSS reversed the effect of DSS on proliferation but not its effect on crypt shortening. COX-1 was expressed in the crypt epithelium and lamina propria mononuclear cells; DSS treatment down-regulated COX-1 expression only in the epithelium. Dimethyl PGE2 reversed the effect of DSS on COX-1 expression. Recovery was associated with a return to normal COX-1 expression in the epithelium. COX-2 was expressed in lamina propria mononuclear cells.


CONCLUSIONS
Epithelial cell proliferation in the presence of DSS contains a PGE2-sensitive component.
Tessner
T G
TG
Division of Gastroenterology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
Cohn
S M
SM
Schloemann
S
S
Stenson
W F
WF
D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology*; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002432:Cecum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D051545:Cyclooxygenase 1; D016264:Dextran Sulfate / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005260:Female; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007527:Isoenzymes / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D008809:Mice, Inbred C3H; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism
D007527:Isoenzymes; D008565:Membrane Proteins; D016264:Dextran Sulfate; D051545:Cyclooxygenase 1; D011451:Prostaglandin-Endoperoxide Synthases; C496512:Ptgs1 protein, mouse; D001973:Bromodeoxyuridine; D015064:16,16-Dimethylprostaglandin E2