Location: Immunity and Disease Prevention ResearchTitle: Inhibition of pattern recognition receptor-mediated inflammation by bioactive phytochemicals) Author
Submitted to: Nutrition Reviews
Publication Type: Review article
Publication Acceptance Date: 12/3/2010
Publication Date: 6/1/2011
Citation: Zhao, L., Lee, J.Y., Hwang, D.H. 2011. Inhibition of pattern recognition receptor-mediated inflammation by bioactive phytochemicals. Nutrition Reviews. 69(6):310-320, DOI: 10.1111/j.1753-4887.2011.00394.x. Interpretive Summary:
Technical Abstract: Emerging evidence reveals that pattern-recognition receptors (PRRs), Toll-like receptors (TLRs) and Nucleotide-binding oligomerization domain proteins (NODs) mediate both infection-induced and sterile inflammation by recognizing pathogen-associated molecular patterns (PAMPs) and endogenous molecules, respectively. PRR-mediated chronic inflammation is an important determinant for the development and progression of chronic diseases including cancer, atherosclerosis and insulin resistance. Recent studies demonstrated that certain bioactive phytochemicals inhibit PRR-mediated pro-inflammatory signaling pathways. Curcumin, helenalin, cinnamaldehyde and sulforaphane, containing a, ß-unsaturated carbonyl or isothiocyanate group, respectively, that are known to interact with free SH groups in cysteine residues, but not resveratrol (with no unsaturated carbonyl group), inhibit TLR4 activation by interfering with TLR4 receptor dimerization. Similarly, curcumin, as well as parthenolide and helenalin containing a, ß-unsaturated carbonyl group, but not resveratrol and EGCG, also inhibits NOD2 activation by interfering with NOD2 dimerization. These results suggest that other phytochemicals containing structural motifs that can modify free SH groups in cysteine residues can inhibit PRR receptor activation through interfering with receptor dimerization. In contrast, resveratrol, EGCG, luteolin and structural analogs of luteolin such as quercetin, chrysin, and eriodictyol, specifically inhibit TLR3 and TLR4 signaling pathway by targeting TBK1 and RIP1 in TRIF complex. Together, these results suggest that PRRs and their downstream signaling components are important molecular targets for dietary strategies to reduce PRR-mediated chronic inflammation and consequent risks of chronic diseases.