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Regulation by prostaglandin E 2 of interleukin release by T lymphocytes in mucosa
Author(s) -
Barrera Susan,
Lai Joyce,
Fiocchi Claudio,
Roche James K.
Publication year - 1996
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/(sici)1097-4652(199601)166:1<130::aid-jcp15>3.0.co;2-j
Subject(s) - prostaglandin e2 , prostaglandin , lymphokine , lamina propria , immune system , prostaglandin d2 , prostaglandin e , lymphocyte , biology , t cell , interleukin 2 , endocrinology , medicine , immunology , epithelium , genetics
Regulation of immune cell activation in lymphocyte‐bearing human tissues is a pivotal host function, and metabolites of arachidonic acid (prostaglandin E 2 in particular) have been reported to serve this function at non‐mucosal sites. However, it is unknown whether prostaglandin E 2 is immunoregulatory for the large lymphocyte population in the lamina propria of intestine; whether low (nM) concentrations of prostaglandin E 2 modulate immune responses occurring there; and whether adjacent inflammation per se abrogates prostaglandin E 2 '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 E 2 concentration range. IL‐3 release by normal intestinal lamina propria mononuclear cells was reduced (up to 78%) in a dose‐dependent manner by prostaglandin E 2 , when present in as low a concentration as 10 −10 M. PGE 2 also inhibited(by ≥ 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 E 2 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 [ 3 H] thymidine uptake studies suggested this was not due to a prostaglandin E 2 ‐induced reduction in T cell proliferation or viability. In contrast, cells from chronically inflamed intestinal mucosa were substantially less sensitive to prostaglandin E 2 , e.g., high concentrations (10 −6 M) of prostaglandin E 2 inhibited IL‐3 release by only 41%. We conclude that prostaglandin E 2 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. © 1996 Wiley‐Liss, Inc.