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标题：Effect of Various Catechins on the IL-12p40 Production by Murine Peritoneal Macrophages and a Macrophage Cell Line, J774.1
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作者：Daiju Ichikawa ; Ayako Matsui ; Miwa Imai 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2004
卷号：27
期号：9
页码：1353-1358
DOI：10.1248/bpb.27.1353
出版社：The Pharmaceutical Society of Japan
摘要：Interleukin-12 (IL-12) is a heterodimeric cytokine comprising p40 and p35 subunits produced mainly by monocytes and macrophages, and plays an essential role in the regulation of the differentiation of Th1 cells. Green tea polyphenols exhibit potent anti-oxidative activities and anti-inflammatory effects by modulating cytokine production. We investigated the effect of catechins on IL-12p40 production in murine macrophages induced by bacterial lipopolysaccharide (LPS). Pretreatment with several catechins at doses of 0.3—30 μ M suppressed IL-12 p40 production by murine peritoneal exudate cells (PEC) and J774.1 cells in a dose-dependent manner. Decreases in protein production were primarily due to down-regulation of the transcription of IL-12p40 mRNA. Of the various catechins, (−)-epigallocatechin gallate (EGCG) was the most potent inhibitor, followed by (−)-gallocatechin gallate (GCG) and (−)-epicatechin gallate (ECG). EGCG inhibited LPS-induced phosphorylation of p38 mitogen-activated protein kinase (MAPK), but not Jun N-terminal kinase (JNK), while EGCG augmented LPS-induced phosphorylation of p44/p42 extracellular signal-related kinase (ERK). In addition, both EGCG and GCG inhibited LPS-induced degradation of IκBα with concomitant inhibition of nuclear protein binding to NF-κB site and synthesis of IRF-1. These results suggest that gallate-containing catechins, particularly EGCG, inhibits LPS-induced IL-12p40 production in murine macrophages by inhibiting p38 MAPK while enhancing p44/p42 ERK, leading to the inhibition of IκBα degradation and NF-κB activation.
关键词：interleukin-12 (IL-12);catechin;(−)-epigallocatechin gallate (EGCG);NF-κB;p38MAP kinase;extracellular signal-related kinase (ERK)