Immunosuppressive effect of leukotriene B(4) receptor antagonist in vitro.
Leukotriene B(4) (LTB(4)), which is an arachidonic acid metabolite produced by the 5-lipoxygenase pathway and a well-characterized chemical mediator of inflammation, has been proposed to be an immune response modulator. Here we showed the constitutive expression of the LTB(4) receptor (LTB(4)R) in resting and activated T cells. We found that the LTB(4)R antagonist inhibited T cell proliferation induced by Con A, immobilized anti-CD3 mAb, or IL-2. This inhibitory effect was abolished by addition of LTB(4)R agonist. The LTB(4)R antagonist inhibited IL-2, IFN-gamma, and IL-4 production by anti-CD3-stimulated T cells and also inhibited IL-12-induced IFN-gamma production. Moreover, the LTB(4)R antagonist exerted an additive inhibitory effect to FK506 on T cell proliferation. These results suggest that LTB(4) is intrinsically involved in T cell activation to upregulate cytokine production and proliferation, and thus the LTB(4)R antagonist might be useful as an immunosuppressive agent.
Morita
H
H
Department of Immunology, Juntendo University School of Medicine, Bunkyou-ku, Tokyo, Japan.
Takeda
K
K
Yagita
H
H
Okumura
K
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000187:drug effects; D002455:Cell Division; D002478:Cells, Cultured; D003208:Concanavalin A / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007371:Interferon-gamma / Q000032:analysis; D007376:Interleukin-2 / Q000032:analysis / Q000494:pharmacology; D015847:Interleukin-4 / Q000032:analysis; D007975:Leukotriene B4 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D010666:Phenylpropionates / Q000494:pharmacology*; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D018102:Receptors, Leukotriene B4 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D016559:Tacrolimus / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D010666:Phenylpropionates; D015375:Receptors, Interleukin-2; D018102:Receptors, Leukotriene B4; C086476:monoclonal mouse globulin IgG2a A1CD3; D003208:Concanavalin A; C067523:ONO-LB 457; D007975:Leukotriene B4; D015847:Interleukin-4; D007371:Interferon-gamma; D016559:Tacrolimus