title: The role of arachidonic acid metabolite PGE2 on T cell proliferative response.
abstract: We have examined the role of cyclooxygenase and lipooxygenase-derived metabolites of arachidonic acid (AA) during T cell activation. One of the major products of cyclooxygenase activity is prostaglandin E2 (PGE2). As is known, macrophages (Mo) are the main PGE2 producer cells among the peripheral blood mononuclear cells (PBL) and can be induced to release PGE2 during T cell activation. On culturing PBL with T cell mitogens such as phytohemagglutinin (PHA) or monoclonal antibody OKT3, the levels of PGE2 produced by Mo were positively correlated with the entity of the T cell mitogenic signal. During T cell activation, subcellular factors able to provide positive or negative signals on the Mo PGE2 production are released in culture. We observed that recombinant IL2 strongly enhanced PGE2 synthesis in lipopolysaccharide (LPS) stimulated Mo culture, while recombinant interferon gamma (IFN-gamma) partially inhibited its production. Moreover, purified IL1 induced PGE2 synthesis in resting Mo and increased its production when Mo were activated by LPS. The PGE2 released during T cell activation seems to have no effect on T cell mitogenesis, since the addition of cyclooxygenase inhibitors did not influence the proliferative response of mitogen stimulated T cells. However, the addition of PGE2 to OKT3 stimulated PBL at the beginning of the culture period inhibited the proliferative response in a dose-dependent manner. Its addition had no effect on PHA-stimulated PBL cultures. The PGE2-dependent inhibition of OKT3-induced T cell proliferation declined progressively from about 50-10% as the addition of PGE2 was delayed from 0 to 24 hr.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Pathology, Università Cattolica S. Cuore, Rome, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Valitutti
authors.forename: F
authors.initials: F
authors.lastname: Castellino
authors.forename: F B
authors.initials: FB
authors.lastname: Aiello
authors.forename: R
authors.initials: R
authors.lastname: Ricci
authors.forename: P
authors.initials: P
authors.lastname: Patrignani
authors.forename: P
authors.initials: P
authors.lastname: Musiani
mesh_terms: D001685:Biological Factors / Q000494:pharmacology; D016207:Cytokines; D015232:Dinoprostone / Q000096:biosynthesis / Q000502:physiology*; D006801:Humans; D016859:Lipoxygenase Inhibitors; D008213:Lymphocyte Activation / Q000502:physiology*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D010835:Phytohemagglutinins / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D047069:Pyrazolones; D013601:T-Lymphocytes / Q000502:physiology*
chemical_list: D001685:Biological Factors; D016207:Cytokines; D016859:Lipoxygenase Inhibitors; D010835:Phytohemagglutinins; D011720:Pyrazoles; D047069:Pyrazolones; D015232:Dinoprostone; C018845:nafazatrom