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

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

来源：Biochemical and Biophysical Research Communications, 2013, 438(1): 122-128.

DOI：10.1016/j.bbrc.2013.07.038

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

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.

• 出版日期2013-8-16