Lymphokine regulation of activated (G1) lymphocytes. I. Prostaglandin E2-induced inhibition of interleukin 2 production.
PGE2-induced inhibition of the proliferatory response of PHA-stimulated human PBL and Con A-stimulated murine thymocytes was analyzed by flow cytometry. It was found that the activation process (G0-G1a transition) was not influenced by PGE2 over a wide range of concentrations (10(-10) to 10(-6) M), nor was the formation of IL 2 receptors inhibited. Similarly, the viability of human lymphocytes was practically unaltered. In contrast, the IL 2-dependent cell cycle event (G1a-G1b transition), which is required for proliferation, was inhibited in a dose-dependent fashion. The addition of IL 2-containing supernatants to such cultures prevented the PGE2-mediated block in the G1a phase and reconstituted a normal lymphocyte proliferation. Furthermore, lower IL 2 titers were measured in supernatants from PHA-stimulated human PBL treated with PGE2. These findings strongly suggest that PGE2 primarily exerts its inhibitory effect on lymphocyte proliferation through an inhibition of IL 2 production.
D000328:Adult; D000818:Animals; D015232:Dinoprostone; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis*; D007399:Interphase; D008213:Lymphocyte Activation / Q000187:drug effects; D008222:Lymphokines / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010835:Phytohemagglutinins / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D007376:Interleukin-2; D008222:Lymphokines; D010835:Phytohemagglutinins; D011458:Prostaglandins E; D015232:Dinoprostone