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.
Drug Discovery I, Pharmaceutical Research Center, Mochida Pharmaceutical Co., Ltd.722 Jimba-aza-Uenohara, Gotemba, Shizuoka 412-8524, Japan. yutakato@mochida.co.jp
Yutaka
Y
Kato
Takaaki
T
Negishi
Shoji
S
Furusako
Kiyoshi
K
Mizuguchi
Hidenori
H
Mochizuki
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