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

The tissue concentration of PGE(2) is heightened during mucosal inflammatio n. 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 quantitat e the four member EP family of prostanoid receptors for binding PGE(2) on c ells of histologically normal and inflamed human colonic mucosa, and then e xamined the physiological consequences for the epithelial component of inte stine, with special attention to its barrier function. Prostanoid receptors were selectively expressed on a limited number of human colonic mucosal ce lls, and differed markedly between normal and inflamed tissue, in non-infla med mucosa, EP2 and EP3 were expressed on epithelia at the apex of crypts; while EP4 was expressed on surface and lateral crypt epithelia. Dual immuno staining and in situ hybridization with digoxygenin-labelled RNA probes lar gely confirmed the epithelial localization of EP4. On the other hand, durin g inflammation, lateral crypt (non-surface) epithelial cells newly and sign ificantly expressed prostanoid receptors EP2 and EP3 (p < 0.05, by computer -assisted densitometry). Functionally, exogenous E series prostanoids appli ed to epithelial monolayers in nM concentrations brought about a 24% increa se in the level of barrier function; an associated rise in intracellular cA MP (EC50 of 281); and protection of epithelium from the effects of T cell c ytokines. A major perturbation in the number and distribution of functional eicosonoid receptors on epithelia occurs in chronic inflammation of human colonic mucosa. (C) 2000 Harcourt Publishers Ltd.