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

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• 作者：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
• 关键词：DTT ; dithiothreitol ; FITC ; fluorescein isothiocyanate ; IFN ; interferon ; I¦Ê-B ; inhibitor of ¦ÊB ; IL ; interleukin ; IRAK ; IL-1 receptor-associated kinase ; LPS ; lipopolysaccharide ; MAPK ; mitogen-activated protein kinase ; MyD88 ; myeloid differentiation factor
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2013
• 出版时间：16 August, 2013
• 年：2013
• 卷：438
• 期：1
• 页码：122-128
• 全文大小：1414 K

文摘

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-¦Á, IL-1¦Â, 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 ¦ÊB and p65 through IRAK-M. We also found that Pro B2-treated macrophages inactivated na?ve T cells by inhibiting LPS-induced interferon-¦Ã 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.