Green Tea Polyphenol EGCG Upregulates Tollip Expression by Suppressing Elf-1 Expression

• Published in: The Journal of immunology (1950) 2017-11, Vol.199 (9), p.3261-3269
• Main Authors: Kumazoe, Motofumi, Yamashita, Mai, Nakamura, Yuki, Takamatsu, Kanako, Bae, Jaehoon, Yamashita, Shuya, Yamada, Shuhei, Onda, Hiroaki, Nojiri, Takashi, Kangawa, Kenji, Tachibana, Hirofumi
• Format: Article
• Language: English
• Subjects: Animals; Catechin - analogs & derivatives; Catechin - chemistry; Catechin - pharmacology; Cyclic GMP; Cyclic GMP - genetics; Cyclic GMP - immunology; Disease resistance; DNA-Binding Proteins - genetics; DNA-Binding Proteins - immunology; Epigallocatechin gallate; ETS protein; Green tea; Immune system; Inflammatory diseases; Innate immunity; Insulin; Intracellular levels; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - immunology; Macrophages; Male; Metastases; Mice; Mice, Inbred BALB C; Nuclear Proteins - genetics; Nuclear Proteins - immunology; Oral administration; Phosphoprotein phosphatase; Protein phosphatase; Protein Phosphatase 2 - genetics; Protein Phosphatase 2 - immunology; Proteins; Second Messenger Systems - genetics; Second Messenger Systems - immunology; Signal transduction; Tea; Tea - chemistry; TLR4 protein; Toll-Like Receptor 4 - genetics; Toll-Like Receptor 4 - immunology; Toll-like receptors; Transcription Factors - genetics; Transcription Factors - immunology; Up-Regulation - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1601822

TLR signaling is critical to innate immune system regulation; however, aberrant TLR signaling is involved in several diseases, including insulin resistance, Alzheimer's disease, and tumor metastasis. Moreover, a recent study found that TLR-4 signaling pathway inhibition might be a target for the suppression of chronic inflammatory disorders. In this article, we show that the green tea polyphenol epigallocatechin-3- -gallate (EGCG) increases the expression of Toll interacting protein, a strong inhibitor of TLR4 signaling, by suppressing the expression of E74-like ETS transcription factor 1 (Elf-1). A mechanistic study revealed that EGCG suppressed Elf-1 expression via protein phosphatase 2A/cyclic GMP (cGMP)-dependent mechanisms. We also confirmed that orally administered EGCG and a cGMP inducer upregulated Toll interacting protein expression, increased intracellular levels of cGMP in macrophages, and suppressed Elf-1 expression. These data support EGCG and a cGMP inducer as potential candidate suppressors of TLR4 signaling.