An orally active Th1/Th2 balance modulator, M50367, suppresses Th2 differentiation of naïve Th cell in vitro.

Abstract

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.

• Authors: Yutaka Kato, Takaaki Negishi, Shoji Furusako, Kiyoshi Mizuguchi, Hidenori Mochizuki
• Journal: Cellular immunology (Cell Immunol) Vol. 224 Issue 1 Pg. 29-37 (Jul 2003) ISSN: 0008-8749 [Print] Netherlands
• PMID: 14572798 (Publication Type: Journal Article)

Chemical References

• Anti-Allergic Agents
• Antibodies
• Antigens
• Benzimidazoles
• M 50367
• Interleukin-4
• Interferon-gamma

Topics

• Administration, Oral
• Animals
• Anti-Allergic Agents (pharmacology)
• Antibodies (immunology, pharmacology)
• Antigen-Presenting Cells (immunology)
• Antigens (immunology, pharmacology)
• Asthma (drug therapy, immunology)
• Benzimidazoles (administration & dosage, pharmacology)
• Cell Differentiation (drug effects, immunology)
• Cell Division (drug effects, immunology)
• Dose-Response Relationship, Drug
• Interferon-gamma (biosynthesis, immunology)
• Interleukin-4 (biosynthesis, immunology)
• Mice
• Mice, Inbred BALB C
• Mice, Transgenic
• Reaction Time (drug effects, immunology)
• Th1 Cells (drug effects, immunology)
• Th2 Cells (drug effects, immunology)