Procyanidin dimer B2-mediated IRAK-M induction negatively regulates TLR4 signaling in macrophages

Nak Yun Sung, Mi So Yang, Du Sub Song, Jae Kyung Kim, Jong Heum Park, Beom Seok Song, Sang Hyun Park, Ju Woon Lee, Hyun Jin Park, Jae Hun Kim, Eui Baek Byun, Eui Hong Byun

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24 Citations (Scopus)

Abstract

Polyphenolic compounds have been found to possess a wide range of physiological activities that may contribute to their beneficial effects against inflammation-related diseases; however, the molecular mechanisms underlying this anti-inflammatory activity are not completely characterized, and many features remain to be elucidated. In this study, we investigated the molecular basis for the down-regulation of toll-like receptor 4 (TLR4) signal transduction by procyanidin dimer B2 (Pro B2) in macrophages. Pro B2 markedly elevated the expression of the interleukin (IL)-1 receptor-associated kinase (IRAK)-M protein, a negative regulator of TLR signaling. Lipopolysaccharide (LPS)-induced expression of cell surface molecules (CD80, CD86, and MHC class I/II) and production of pro-inflammatory cytokines (tumor necrosis factor-α, IL-1β, IL-6, and IL-12p70) were inhibited by Pro B2, and this action was prevented by IRAK-M silencing. In addition, Pro B2-treated macrophages inhibited LPS-induced activation of mitogen-activated protein kinases such as extracellular signal-regulated kinase 1/2, p38, and c-Jun N-terminal kinase and the translocation of nuclear factor κB and p65 through IRAK-M. We also found that Pro B2-treated macrophages inactivated naïve T cells by inhibiting LPS-induced interferon-γ and IL-2 secretion through IRAK-M. These novel findings provide new insights into the understanding of negative regulatory mechanisms of the TLR4 signaling pathway and the immune-pharmacological role of Pro B2 in the immune response against the development and progression of many chronic diseases.

Original languageEnglish
Pages (from-to)122-128
Number of pages7
JournalBiochemical and biophysical research communications
Volume438
Issue number1
DOIs
Publication statusPublished - 2013 Aug 16

Keywords

  • Cytokine
  • Mitogen-activated protein kinases
  • Nuclear factor κB
  • Procyanidin B2
  • Toll-like receptor

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Sung, N. Y., Yang, M. S., Song, D. S., Kim, J. K., Park, J. H., Song, B. S., Park, S. H., Lee, J. W., Park, H. J., Kim, J. H., Byun, E. B., & Byun, E. H. (2013). Procyanidin dimer B2-mediated IRAK-M induction negatively regulates TLR4 signaling in macrophages. Biochemical and biophysical research communications, 438(1), 122-128. https://doi.org/10.1016/j.bbrc.2013.07.038