Regular Article
Prostanoid receptors in intestinal epithelium: selective expression, function, and change with inflammation

https://doi.org/10.1054/plef.2000.0144Get rights and content

Abstract

The tissue concentration of PGE2is heightened during mucosal inflammation. Nevertheless, the cellular targets of this prostanoid and its effects on epithelial cell physiology are incompletely understood. We used a panel of specific immunoglobulin and mRNA probes in order to localize and quantitate the four member EP family of prostanoid receptors for binding PGE2on cells of histologically normal and inflamed human colonic mucosa, and then examined the physiological consequences for the epithelial component of intestine, with special attention to its barrier function. Prostanoid receptors were selectively expressed on a limited number of human colonic mucosal cells, and differed markedly between normal and inflamed tissue. In non-inflamed mucosa, EP2and EP3were expressed on epithelia at the apex of crypts; while EP4was expressed on surface and lateral crypt epithelia. Dual immunostaining and in situ hybridization with digoxygenin-labelled RNA probes largely confirmed the epithelial localization of EP4. On the other hand, during inflammation, lateral crypt (non-surface) epithelial cells newly and significantly expressed prostanoid receptors EP2and EP3(p<0.05, by computer-assisted densitometry). Functionally, exogenous E series prostanoids applied to epithelial monolayers in nM concentrations brought about a 24% increase in the level of barrier function; an associated rise in intracellular cAMP (EC50of 281); and protection of epithelium from the effects of T cell cytokines. A major perturbation in the number and distribution of functional eicosonoid receptors on epithelia occurs in chronic inflammation of human colonic mucosa.

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    Grant support: Supported in part by a grant from NCl, National Institute of Health (CA68226) and by the Crohn's and Colitis Foundation of America.

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    Correspondence to: James K. Roche, MD, PhD, Box 1005, MR-4 Building, UVA Health Sciences Center, Charlottesville, VA 22908, USA. Tel.: +804 243 2655; Fax: +804 243 6169; E-mail: [email protected]

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