Suppression of homodimerization of toll-like receptor 4 by isoliquiritigenin.
Toll-like receptors (TLRs) play important inductive roles in innate immune responses for host defense against invading microbial pathogens. Activation of TLR4 by lipopolysaccharide (LPS) induces dimerization of TLR4 and, subsequently, activation of downstream signaling pathways including nuclear factor-kappa B and interferon regulatory factor 3. TLR4 dimerization may be an early regulatory event in activating signaling pathways induced by LPS. Here, biochemical evidence is reported that isoliquiritigenin, one of the major ingredients derived from licorice root, inhibits LPS-induced TLR4 dimerization resulting in inhibition of nuclear factor-kappa B and interferon regulatory factor 3 activation, and cyclooxygenase-2 and inducible nitric oxide synthase expression. These results suggest that isoliquiritigenin modulates TLR-mediated signaling pathways at the receptor level. Furthermore, these results suggest that TLRs themselves may be important targets for the prevention of chronic inflammatory diseases.
Park
Se-Jeong
SJ
Department of Medical Science, College of Medical Sciences, Soonchunhyang University, Asan-Si, Chungnam, Republic of Korea.
Youn
Hyung-Sun
HS
D000818:Animals; D047188:Chalcones / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000187:drug effects; D006035:Glycyrrhiza / Q000737:chemistry; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000037:antagonists & inhibitors; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D052247:Nitric Oxide Synthase Type II / Q000187:drug effects; D018517:Plant Roots / Q000737:chemistry; D051197:Toll-Like Receptor 4 / Q000187:drug effects* / Q000378:metabolism
D047188:Chalcones; C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; D008070:Lipopolysaccharides; D016328:NF-kappa B; D051197:Toll-Like Receptor 4; C040920:isoliquiritigenin; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2