کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1928967 | 1050437 | 2013 | 8 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Quercetin negatively regulates TLR4 signaling induced by lipopolysaccharide through Tollip expression Quercetin negatively regulates TLR4 signaling induced by lipopolysaccharide through Tollip expression](/preview/png/1928967.png)
Polyphenolic compounds have been regarded as one of the most promising dietary agents for the prevention and treatment of inflammation-related chronic diseases; however, the anti-inflammatory activities of flavonoids, such as quercetin, are not completely characterized, and many features remain to be elucidated. In this study, we showed the molecular basis for the downregulation of TLR4 signal transduction by quercetin. Quercetin markedly elevated the expression of the Toll-interacting protein, a negative regulator of TLR signaling. Lipopolysaccharide-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 quercetin, and this action was prevented by Toll-interacting protein silencing. In addition, quercetin-treated macrophages inhibited lipopolysaccharide-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 Toll-interacting protein. Treatment with quercetin resulted in a significant decrease in prostaglandin E2 and cyclooxygenase-2 levels as well as inducible nitric oxide synthase-mediated nitric oxide production induced by lipopolysaccharide. Taken together, these findings represent new insights into the understanding of negative regulatory mechanisms of the TLR4 signaling pathway and effective therapeutic intervention for the treatment of inflammatory disease.
► Quercetin markedly elevated the expression of the Toll-interacting protein.
► LPS-induced expression of cell surface molecules was inhibited by quercetin.
► LPS-induced pro-inflammatory cytokines were inhibited by quercetin.
► Quercetin inhibited MAPKs and NF-κB signaling via Toll-interacting protein.
Journal: Biochemical and Biophysical Research Communications - Volume 431, Issue 4, 22 February 2013, Pages 698–705