Cell action mechanism of tranilast--effect on the expression of HLA-class II antigen.
We tested the effect of Tranilast [N-(3',4'-dimethoxycinnamoyl anthranilic acid)], one of the anti-allergic agents, on the induction of interleukin 2 (IL2) responsiveness of lymphocytes from patients with bronchial asthma or hen-egg allergy following stimulation with Dermatophagoides farinae (Df) or ovalbumin (OVA), respectively. Mononuclear cells pretreated with Tranilast for 12 h failed to respond to IL2 following incubation with Df or OVA. Also Tranilast inhibited purified protein derivative (PPD)-induced IL2 responsiveness of normal lymphocytes but not the Con A-induced IL2 responsiveness of normal or allergen-sensitized lymphocytes. These results suggested that Tranilast has some immunosuppressive effect in that it inhibits antigen-induced IL2 responsiveness. Separation of potential target cells of Tranilast disclosed that antigen-presenting adherent cells were more susceptible to Tranilast than IL2-responding T-cell rich populations. Expression of HLA-DR and -DQ antigens but not DP antigens on macrophages, was significantly suppressed by treatment with Tranilast, although Tranilast scarcely decreased HLA class II antigens expression on B-cells. The suppression was overcome by interferon-gamma, which was known as an inducer for class II antigen expression. Taken together, Tranilast may suppress antigen-induced IL2 responsiveness by inhibiting HLA-DR and HLA-DQ antigens on macrophages.
Kawano
Y
Y
Department of Pediatrics, Saitama Medical School, Japan.
Noma
T
T
D000328:Adult; D000818:Animals; D039741:Antigens, Dermatophagoides; D001249:Asthma / Q000276:immunology; D002675:Child, Preschool; D005512:Food Hypersensitivity / Q000276:immunology; D006023:Glycoproteins; D006681:HLA-D Antigens / Q000378:metabolism*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007223:Infant; D007376:Interleukin-2 / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008925:Mites / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
D039741:Antigens, Dermatophagoides; D006023:Glycoproteins; D006681:HLA-D Antigens; D006634:Histamine H1 Antagonists; D007376:Interleukin-2; D062367:ortho-Aminobenzoates; D010047:Ovalbumin; C012293:tranilast