title: Regulation by prostaglandin E2 of interleukin release by T lymphocytes in mucosa.
abstract: Regulation of immune cell activation in lymphocyte-bearing human tissues is a pivotal host function, and metabolites of arachidonic acid (prostaglandin E2 in particular) have been reported to serve this function at non-mucosal sites. However, it is unknown whether prostaglandin E2 is immunoregulatory for the large lymphocyte population in the lamina propria of intestine; whether low (nM) concentrations of prostaglandin E2 modulate immune responses occurring there; and whether adjacent inflammation per se abrogates prostaglandin E2's regulatory effects. To address these issues, intestine-derived lymphocytes and T hybridoma cells were assessed, T cell activation was monitored by release of independently quantitated lymphokines, and dose-response studies were performed over an 8-log prostaglandin E2 concentration range. IL-3 release by normal intestinal lamina propria mononuclear cells was reduced (up to 78%) in a dose-dependent manner by prostaglandin E2, when present in as low a concentration as 10(-10) M. PGE2 also inhibited (by > or = 60%) mucosal T lymphocytes' ability to destabilize the barrier function of human epithelial monolayers. Further, with an intestine-derived T lymphocyte hybridoma cell line, a prostaglandin E2 dose-dependent reduction in IL-3 and IL-2 (90 and 95%, respectively) was found; this was true for both mitogen- and antigen-driven T cell lymphokine release. Concomitant [3H] thymidine uptake studies suggested this was not due to a prostaglandin E2-induced reduction in T cell proliferation or viability. In contrast, cells from chronically inflamed intestinal mucosa were substantially less sensitive to prostaglandin E2, e.g., high concentrations (10(-6) M) of prostaglandin E2 inhibited IL-3 release by only 41%. We conclude that prostaglandin E2 in nM concentrations is an important modulator of cytokine release from T lymphocytes derived from the gastrointestinal tract, and it may play a central role in regulation of lamina propria immunocyte populations residing there.
authors.affiliation: Department of Internal Medicine, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
authors.forename: S
authors.initials: S
authors.lastname: Barrera
authors.forename: J
authors.initials: J
authors.lastname: Lai
authors.forename: C
authors.initials: C
authors.lastname: Fiocchi
authors.forename: J K
authors.initials: JK
authors.lastname: Roche
mesh_terms: D000818:Animals; D002460:Cell Line / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D003106:Colon / Q000166:cytology / Q000276:immunology; D003424:Crohn Disease / Q000276:immunology / Q000473:pathology; D015232:Dinoprostone / Q000502:physiology*; D004847:Epithelial Cells; D004848:Epithelium / Q000196:embryology / Q000276:immunology; D006801:Humans; D006825:Hybridomas; D007376:Interleukin-2 / Q000378:metabolism*; D007377:Interleukin-3 / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D010047:Ovalbumin / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism; D014316:Tritium / Q000378:metabolism
chemical_list: D007376:Interleukin-2; D007377:Interleukin-3; D014316:Tritium; D010047:Ovalbumin; D015232:Dinoprostone; D013936:Thymidine