Effect of various catechins on the IL-12p40 production by murine peritoneal macrophages and a macrophage cell line, J774.1

Daijyu Ichikawa, Ayako Matsui, Miwa Imai, Yoshiko Sonoda, Tadashi Kasahara

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

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 μM 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.

Original languageEnglish
Pages (from-to)1353-1358
Number of pages6
JournalBiological and Pharmaceutical Bulletin
Volume27
Issue number9
DOIs
Publication statusPublished - 2004 Sep
Externally publishedYes

Fingerprint

Interleukin-12 Subunit p40
Catechin
Peritoneal Macrophages
Lipopolysaccharides
Macrophages
Cell Line
Phosphotransferases
p38 Mitogen-Activated Protein Kinases
Interleukin-12
Phosphorylation
Cytokines
Th1 Cells
Polyphenols
Tea
Exudates and Transudates
Nuclear Proteins
Protein Binding
Monocytes
Anti-Inflammatory Agents
Down-Regulation

Keywords

  • (-)-epigallocatechin gallate (EGCG)
  • Catechin
  • Extracellular signal-related kinase (ERK)
  • Interleukin-12 (IL-12)
  • NF-κB
  • p38MAP kinase

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

Cite this

Effect of various catechins on the IL-12p40 production by murine peritoneal macrophages and a macrophage cell line, J774.1. / Ichikawa, Daijyu; Matsui, Ayako; Imai, Miwa; Sonoda, Yoshiko; Kasahara, Tadashi.

In: Biological and Pharmaceutical Bulletin, Vol. 27, No. 9, 09.2004, p. 1353-1358.

Research output: Contribution to journalArticle

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AU - Ichikawa, Daijyu

AU - Matsui, Ayako

AU - Imai, Miwa

AU - Sonoda, Yoshiko

AU - Kasahara, Tadashi

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