Immunomodulatory effect of the antiasthma Chinese herbal formula MSSM-002 on T_H2 cells

Background: T_H2 cytokines play a central role in the pathogenesis of allergic asthma. We previously showed that the "antiasthma" Chinese herbal formula MSSM-002 exhibited therapeutic effects on established allergic airway responses in a murine model of allergic asthma. However, the mechanisms underlying these effects are largely unknown. Objective: The objective of this study was to determine whether and how MSSM-002 modulates an established T_H2 response and whether the actions of MSSM-002 on T_H2 cell differs from corticosteroids. Methods: T_H2 polarized splenocytes (T_H2-SPCs) from mice with antigen-induced airway hyperresponsiveness and T_H2 cloned cells, D10 G4.1 (D10), were cultured in the presence or absence of antigen with or without MSSM-002 and dexamethasone, and the proliferative responses and cytokine profiles were determined. Apoptosis and T_H2 transcription factor GATA-3 expression and binding to IL-4 gene promoter and V_A enhancer in MSSM-002-treated D10 cells were also determined. Results: MSSM-002 significantly decreased antigen-induced proliferation and IL-4 and IL-S production but increased IFN-γ production by T_H2-SPCs, whereas dexamethasone suppressed IFN-γ as well as IL-4 and IL-5. Anti-IL-12 antibody, although abrogating MSSM-002 induction of IFN-γ, had no significant effect on MSSM-002 suppression of IL-4 and IL-5 secretion. MSSM-002 also suppressed T_H2 cytokine secretion by D10 cells, and in contrast to dexamethasone, MSSM-002 did not induce apoptosis of D10 cells. MSSM-002 markedly suppressed GATA-3 mRNA and protein expression and the binding to IL-4 gene promoter and VA enhancer in D10 cells. Conclusion: MSSM-002, in contrast to the overall suppression ofT cells by dexamethasone, exhibits immunomodulatory actions on T_H2 cells caused, at least partially, by downregulation of GATA-3.