Inhibition of homodimerization of toll-like receptor 4 by 6-shogaol.
Toll-like receptors (TLRs) play a critical role in sensing microbial components and inducing innate immune and inflammatory responses by recognizing invading microbial pathogens. Lipopolysaccharide-induced dimerization of TLR4 is required for the activation of downstream signaling pathways including nuclear factor-kappa B (NF-kappaB). Therefore, TLR4 dimerization may be an early regulatory event in activating ligand-induced signaling pathways and induction of subsequent immune responses. Here, we report biochemical evidence that 6-shogaol, the most bioactive component of ginger, inhibits lipopolysaccharide-induced dimerization of TLR4 resulting in the inhibition of NF-kappaB activation and the expression of cyclooxygenase-2. Furthermore, we demonstrate that 6-shogaol can directly inhibit TLR-mediated signaling pathways at the receptor level. These results suggest that 6-shogaol can modulate TLR-mediated inflammatory responses, which may influence the risk of chronic inflammatory diseases.
Ahn
Sang-Il
SI
Department of Biomedical Laboratory Science, College of Medical Sciences, Soonchunhyang University, Asan, 336-745, Korea.
Lee
Jun-Kyung
JK
Youn
Hyung-Sun
HS
D000818:Animals; D002396:Catechols / Q000494:pharmacology*; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D019281:Dimerization; D015151:Immunoblotting; D047468:Immunoprecipitation; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009153:Mutagens / Q000494:pharmacology*; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D010957:Plasmids; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D014162:Transfection
D002396:Catechols; D008070:Lipopolysaccharides; C507779:MYD88 protein, human; D009153:Mutagens; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D010936:Plant Extracts; D051197:Toll-Like Receptor 4; C040115:shogaol; D008156:Luciferases; D051546:Cyclooxygenase 2