An orally active Th1/Th2 balance modulator, M50367, suppresses Th2 differentiation of naïve Th cell in vitro.
We previously reported an orally active anti-allergic agent, M50367, modulated Th1/Th2 balance to down-regulate Th2 response in a murine model of atopic asthma. In this study, we examined the effect of M50354, the active metabolite of M50367, on the differentiation of naïve Th cells into Th1/Th2 cells. M50354 at 3 microM decreased the generation of Th2 cells by 0.2-fold and increased that of Th1 cells by 1.6-fold from naïve Th cells primed with antigenic peptide and antigen-presenting cells. Its effect was also seen when naïve Th cells were primed with anti-T cell receptor and anti-CD28 agonistic antibodies instead of antigen and antigen-presenting cells. M50354 decreased early endogenous IL-4 production in the nai;ve Th cell priming culture without affecting interferon-gamma production and proliferation. In contrast, M50354 had no effect on interferon-gamma and IL-4 production from mature Th1 and Th2 cells. These results suggest that M50354 directly acts on naïve Th cells to suppress their differentiation into Th2 cells.
Kato
Yutaka
Y
Drug Discovery I, Pharmaceutical Research Center, Mochida Pharmaceutical Co., Ltd.722 Jimba-aza-Uenohara, Gotemba, Shizuoka 412-8524, Japan. yutakato@mochida.co.jp
Negishi
Takaaki
T
Furusako
Shoji
S
Mizuguchi
Kiyoshi
K
Mochizuki
Hidenori
H
D000284:Administration, Oral; D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D000938:Antigen-Presenting Cells / Q000276:immunology; D000941:Antigens / Q000276:immunology / Q000494:pharmacology; D001249:Asthma / Q000188:drug therapy / Q000276:immunology; D001562:Benzimidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects* / Q000276:immunology; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D011930:Reaction Time / Q000187:drug effects / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology
D018926:Anti-Allergic Agents; D000906:Antibodies; D000941:Antigens; D001562:Benzimidazoles; C119626:M 50367; D015847:Interleukin-4; D007371:Interferon-gamma