By. Kang et al., Inhibition of interleukin-12 and interferon-gamma production in immune cells by tanshinones from Salvia miltiorrhiza, IMMUNOPHARM, 49(3), 2000, pp. 355-361
Pharmacological control of interleukin-12 (IL-12) and interferon-gamma (IFN
-gamma) production may be a key therapeutic strategy for modulating immunol
ogical diseases dominated by Th1-derived cytokine responses. In this study,
we investigated the effects of three different tanshinone pigments from Sa
lvia miltiorrhiza (tanshinone I, dihydrotanshinone, and cryptotanshinone) o
n IL-12 production in mouse macrophages and on IFN-gamma production in lymp
h node cells. All tested tanshinones significantly inhibited IL-12 producti
on in lipopolysaccharide (LPS)-activated macrophages and also IFN-gamma pro
duction in keyhole limpet hemocyanin (KLH)-primed lymph node cells in a dos
e-dependent manner. Dihydrotanshinone was more effective than tanshinone I
or cryptotanshinone. Tanshinones significantly inhibited the expression of
IL-12 p40 gene at the mRNA level. Furthermore, tanshinones potently inhibit
ed the promoter activation of IL-12 p40 gene and nuclear factor (NF)-kappa
B binding to the kappa B Site, suggesting that tanshinones may negatively r
egulate IL-12 production at the transcription level. These results may expl
ain some known biological activities of tanshinones including their anti-in
flammatory effect, and suggest a possible use of tanshinones in the treatme
nt of immunological diseases dominated by Th1-derived cytokine responses. (
C) 2000 Elsevier Science B.V. All rights reserved.