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

Area of Science:

• Gastroenterology
• Immunology
• Molecular Biology

Background:

• Tissue concentration of prostaglandin E2 (PGE2) increases during mucosal inflammation.
• Cellular targets and physiological effects of PGE2 on epithelial cells remain unclear.

Purpose of the Study:

• To investigate the localization and expression of EP prostanoid receptors in normal and inflamed human colonic mucosa.
• To determine the physiological consequences of these receptors on epithelial barrier function.

Main Methods:

• Utilized immunoglobulin and mRNA probes for localization and quantification of EP receptor family members (EP2, EP3, EP4).
• Examined normal and inflamed human colonic mucosa using immunostaining and in situ hybridization.
• Assessed epithelial barrier function and intracellular cAMP levels in response to E series prostanoids.

Main Results:

• Prostanoid receptors showed selective expression on specific colonic mucosal cells, differing between normal and inflamed tissues.
• In inflamed mucosa, lateral crypt epithelial cells newly expressed EP(2) and EP(3) receptors.
• Exogenous E series prostanoids increased epithelial barrier function by 24%, raised intracellular cAMP, and protected against T cell cytokine effects.

Conclusions:

• A significant alteration in the number and distribution of functional eicosanoid receptors occurs in chronic colonic inflammation.
• These receptor changes likely play a role in modulating epithelial physiology and barrier function during inflammation.