Immunomodulatory effect of the antiasthma Chinese herbal formula MSSM-002 on TH2 cells.
BACKGROUND
T(H)2 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(H)2 response and whether the actions of MSSM-002 on T(H)2 cell differs from corticosteroids.


METHODS
T(H)2 polarized splenocytes (T(H)2-SPCs) from mice with antigen-induced airway hyperresponsiveness and T(H)2 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(H)2 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-5 production but increased IFN-gamma production by T(H)2-SPCs, whereas dexamethasone suppressed IFN-gamma as well as IL-4 and IL-5. Anti-IL-12 antibody, although abrogating MSSM-002 induction of IFN-gamma, had no significant effect on MSSM-002 suppression of IL-4 and IL-5 secretion. MSSM-002 also suppressed T(H)2 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 V(A) enhancer in D10 cells.


CONCLUSIONS
MSSM-002, in contrast to the overall suppression of T cells by dexamethasone, exhibits immunomodulatory actions on T(H)2 cells caused, at least partially, by downregulation of GATA-3.
Srivastava
Kamal
K
Department of Pediatrics, Mount Sinai School of Medicine, New York, NY, USA.
Teper
Ariel A
AA
Zhang
Teng-Fei
TF
Li
Side
S
Walsh
Martin J
MJ
Huang
Chih-Kang
CK
Kattan
Meyer
M
Schofield
Brian H
BH
Sampson
Hugh A
HA
Li
Xiu-Min
XM
D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000941:Antigens / Q000494:pharmacology; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000188:drug therapy* / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D050990:GATA3 Transcription Factor; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000188:drug therapy* / Q000276:immunology; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D008806:Mice, Inbred AKR; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology*; D015534:Trans-Activators / Q000187:drug effects / Q000378:metabolism
D018927:Anti-Asthmatic Agents; D000941:Antigens; D016207:Cytokines; D004268:DNA-Binding Proteins; D004365:Drugs, Chinese Herbal; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; C494748:Gata3 protein, mouse; D005938:Glucocorticoids; D015534:Trans-Activators; D003907:Dexamethasone