Inhibition of interleukin-12 and interferon-gamma production in immune cells by tanshinones from Salvia miltiorrhiza.
Pharmacological control of interleukin-12 (IL-12) and interferon-gamma (IFN-gamma) production may be a key therapeutic strategy for modulating immunological diseases dominated by Th1-derived cytokine responses. In this study, we investigated the effects of three different tanshinone pigments from Salvia miltiorrhiza (tanshinone I, dihydrotanshinone, and cryptotanshinone) on IL-12 production in mouse macrophages and on IFN-gamma production in lymph node cells. All tested tanshinones significantly inhibited IL-12 production in lipopolysaccharide (LPS)-activated macrophages and also IFN-gamma production in keyhole limpet hemocyanin (KLH)-primed lymph node cells in a dose-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 inhibited the promoter activation of IL-12 p40 gene and nuclear factor (NF)-kappaB binding to the kappaB site, suggesting that tanshinones may negatively regulate IL-12 production at the transcription level. These results may explain some known biological activities of tanshinones including their anti-inflammatory effect, and suggest a possible use of tanshinones in the treatment of immunological diseases dominated by Th1-derived cytokine responses.
Kang
B Y
BY
College of Pharmacy, Chonnam National University, 500-757, Kwangju, South Korea.
Chung
S W
SW
Kim
S H
SH
Ryu
S Y
SY
Kim
T S
TS
D045784:Abietanes; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007371:Interferon-gamma / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D018664:Interleukin-12 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D008198:Lymph Nodes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008811:Mice, Inbred DBA; D010616:Phenanthrenes / Q000494:pharmacology*; D010936:Plant Extracts; D027561:Salvia miltiorrhiza
D045784:Abietanes; D004365:Drugs, Chinese Herbal; D007166:Immunosuppressive Agents; D010616:Phenanthrenes; D010936:Plant Extracts; C021751:tanshinone; D018664:Interleukin-12; D007371:Interferon-gamma