Impaired mucosal defense to acute colonic injury in mice lacking cyclooxygenase-1 or cyclooxygenase-2

Olivier Morteau; Scott G Morham; Rance Sellon; Levinus A Dieleman; Robert Langenbach; Oliver Smithies; R. Balfour Sartor

doi:10.1172/JCI6899

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Impaired mucosal defense to acute colonic injury in mice lacking cyclooxygenase-1 or cyclooxygenase-2

Journal article

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Impaired mucosal defense to acute colonic injury in mice lacking cyclooxygenase-1 or cyclooxygenase-2

Olivier Morteau, Scott G Morham, Rance Sellon, Levinus A Dieleman, Robert Langenbach, Oliver Smithies and R. Balfour Sartor

The Journal of clinical investigation, Vol.105(4), pp.469-478

02/15/2000

DOI: https://doi.org/10.1172/JCI6899

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https://hdl.handle.net/2376/109766

PMCID: PMC289156

PMID: 10683376

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Abstract

To investigate roles in intestinal inflammation for the 2 cyclooxygenase (COX) isoforms, we determined susceptibility to spontaneous and induced acute colitis in mice lacking either the COX-1 or COX-2 isoform. We treated wild-type, COX-1 –/– , COX-2 –/– , and heterozygous mice with dextran sodium sulfate (DSS) to provoke acute colonic inflammation, and we quantified tissue damage, prostaglandin (PG) E 2 , and interleukin-1β. No spontaneous gastrointestinal inflammation was detected in mice homozygous for either mutation, despite almost undetectable basal intestinal PGE 2 production in COX-1 –/– mice. Both COX-1 –/– and COX-2 –/– mice showed increased susceptibility to a low-dose of DSS that caused mild colonic epithelial injury in wild-type mice. COX-2 –/– mice were more susceptible than COX-1 –/– mice, and selective pharmacologic blockade of COX-2 potentiated injury in COX-1 –/– mice. At a high dose, DSS treatment was fatal to 50% of the animals in each mutant group, but all wild-type mice survived. DSS treatment increased PGE 2 intestinal secretion in all groups except COX-2 –/– mice. These results demonstrate that COX-1 and COX-2 share a crucial role in the defense of the intestinal mucosa (with inducible COX-2 being perhaps more active during inflammation) and that neither isoform is essential in maintaining mucosal homeostasis in the absence of injurious stimuli.

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Title: Impaired mucosal defense to acute colonic injury in mice lacking cyclooxygenase-1 or cyclooxygenase-2
Creators: Olivier Morteau - Department of Medicine, and
Scott G Morham - Department of Medicine, and
Rance Sellon - Department of Medicine, and
Levinus A Dieleman - Department of Medicine, and
Robert Langenbach - Department of Medicine, and
Oliver Smithies - Department of Medicine, and
R. Balfour Sartor - Department of Medicine, and
Publication Details: The Journal of clinical investigation, Vol.105(4), pp.469-478
Academic Unit: Veterinary Clinical Sciences, Department of
Publisher: American Society for Clinical Investigation
Identifiers: 99900547013701842
Language: English
Resource Type: Journal article