Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 438, Issue 1, Pages 122-128Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2013.07.038
Keywords
Procyanidin B2; Toll-like receptor; Cytokine; Mitogen-activated protein kinases; Nuclear factor kappa B
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Funding
- Basic Research Support Program of the Korea Atomic Energy Research Institute
- Nuclear Research & Development Program of the Korea Science and Engineering Foundation
- Government of the Republic of Korea
- National Research Foundation (NRF) of Korea
- Ministry of Education, Science and Technology [NRF- 2012R1A1A2 009507]
- Kongju National University
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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 82 (Pro 82) 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-alpha, IL-1 beta, 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 kappa B and p65 through IRAK-M. We also found that Pro B2-treated macrophages inactivated naive T cells by inhibiting LPS-induced interferon-gamma 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 82 in the immune response against the development and progression of many chronic diseases. (C) 2013 Elsevier Inc. All rights reserved.
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