Effect of various catechins on the IL-12p40 production by murine peritoneal macrophages and a macrophage cell line, J774.1
Effect of various catechins on the IL-12p40 production by murine peritoneal macrophages and a macrophage cell line, J774.1
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DOI：
10.1248/bpb.27.1353
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发表时间：
2004-09-01
影响因子：
2
通讯作者：
Kasahara, T
中科院分区：
文献类型：
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作者：
Ichikawa, D;Matsui, A;Kasahara, T
白介素12(IL-12)是一种由p40和p35亚基组成的异源二聚体细胞因子，主要由单核细胞和巨噬细胞产生，在Th1细胞分化的调节中起重要作用。绿茶多酚通过调节细胞因子的产生而显示出强大的抗氧化活性和抗炎作用。研究了儿茶素对细菌脂多糖(LPS)诱导的小鼠巨噬细胞产生IL-12p40的影响。几种儿茶素在0.3-30微米剂量下可剂量依赖性地抑制小鼠腹膜渗出细胞(PEC)和J774.1细胞产生IL-12p40。蛋白质产量的减少主要是由于IL-12p40 mRNA转录下调所致。在各种儿茶素中，表没食子儿茶素没食子酸酯(EGCG)的抑制作用最强，其次是(-)表没食子儿茶素没食子酸酯(GCG)和(-)表没食子儿茶素没食子酸酯(CG)。EGCG抑制脂多糖诱导的p38丝裂原活化蛋白激酶(MAPK)的磷酸化，但不抑制Jun氨基末端激酶(JNK)的磷酸化，而EGCG则增强脂多糖诱导的p44/p42胞外信号相关激酶(ERK)的磷酸化。此外，EGCG和GCG均可抑制脂多糖诱导的IkappaBalpha的降解，同时抑制核蛋白与核因子-kappaB结合和IRF-1的合成。这些结果表明，含儿茶素没食子酸酯，尤其是EGCG，通过抑制p38MAPK而增强p44/p42ERK，从而抑制脂多糖诱导的小鼠巨噬细胞IL-12p40的产生，从而抑制IkappaBalpha的降解和核因子-kappaB的激活。
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 muM suppressed IL-12p40 production by murine peritonea[ 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 IkappaBalpha with concomitant inhibition of nuclear protein binding to NF-kappaB 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 IkappaBalpha degradation and NF-kappaB activation.