Gastroenterology

Gastroenterology

Volume 115, Issue 4, October 1998, Pages 874-882
Gastroenterology

Alimentary Tract
Prostaglandins prevent decreased epithelial cell proliferation associated with dextran sodium sulfate injury in mice,☆☆

https://doi.org/10.1016/S0016-5085(98)70259-8Get rights and content

Abstract

Background & Aims: 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.

GASTROENTEROLOGY 1998;115:874-882

Section snippets

Materials

Female C3H/HeJ or C3H/HeN mice were obtained from Jackson Laboratories (Bar Harbor, ME), Taconic (Germantown, NY), or Harlan Sprague–Dawley (Indianapolis, IN); housed in clear plastic cages; and fed a standard laboratory chow diet and water ad libitum. DSS (40,000-50,000 mol wt) was obtained from United States Biochemical (Cleveland, OH). Indomethacin, bromodeoxyuridine (BrdUrd), flurodeoxyuridine, and dmPGE2 were obtained from Sigma Chemical Co. (St. Louis, MO) and NS-398 from Biomol (Plymouth

Results

Administration of 3% DSS in the drinking water of female C3H mice for 5 days reproducibly resulted in injury that healed when the DSS was removed from the drinking water. The injury was characterized by blood in the stool, a loss of normal crypt architecture, thickening and edema of the muscularis (Figure 1), and patchy ulceration.

. DSS induces colitis in mice. Mice were treated for 5 days with 3% DSS in their drinking water. Cecal tissue was preserved in Bouin's fixative, sectioned, and stained

Discussion

The molecular mechanisms underlying the pathology of human IBD and DSS-induced colitis, which is a model for human IBD, remain unclear. Therefore, investigations regarding the mechanism of DSS-induced colitis are important not only for their potential applicability to human disease but in light of the common use of this model system. In our study we found two DSS-induced changes in the cecal epithelium: diminished proliferation and crypt shortening. DSS-induced crypt shortening in the cecum was

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    Address requests for reprints to: Teresa G. Tessner, Ph.D., Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8124, St. Louis, Missouri 63110. Fax: (314) 362-8959.

    ☆☆

    Supported by R01-DK33165 from the National Institutes of Health, by a grant from the Crohn's and Colitis Foundation of America (to W.F.S.), and by T32 DK07130-22 from the National Institutes of Health. (to T.G.T.).

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