Suppression of the TRIF-dependent signaling pathway of toll-like receptors by isoliquiritigenin in RAW264.7 macrophages.
Toll-like receptors (TLRs) play an important role in host defense by sensing invading microbial pathogens and initiating innate immune responses. The stimulation of TLRs by microbial components triggers the activation of myeloid differential factor 88 (MyD88)- and toll-interleukin-1 receptor domain-containing adapter inducing interferon-beta (TRIF)-dependent downstream signaling pathways. Isoliquiritigen in (ILG), an active ingredient of Licorice, has been used for centuries to treat many chronic diseases. ILG inhibits the MyD88-dependent pathway by inhibiting the activity of inhibitor-kappaB kinase. However, it is not known whether ILG inhibits the TRIF-dependent pathway. To evaluate the therapeutic potential of ILG, we examined its effect on signal transduction via the TRIF-dependent pathway of TLRs induced by several agonists. ILG inhibited nuclear factor-kappaB and interferon regulatory factor 3 activation induced by lipopolysaccharide or polyinosinic-polycytidylic acid. ILG inhibited the lipopolysaccharide-induced phosphorylation of interferon regulatory factor 3 as well as interferon-inducible genes such as interferon inducible protein-10, and regulated activation of normal T-cell expressed and secreted (RANTES). These results suggest that ILG can modulate TRIF-dependent signaling pathways of TLRs, leading to decreased inflammatory gene expression.
Park
Se-Jeong
SJ
Department of Medical Science, College of Medical Sciences, Soonchunhyang University, Asan 336-745, Korea.
Song
Ho-Yeon
HY
Youn
Hyung-Sun
HS
D033942:Adaptor Proteins, Vesicular Transport / Q000037:antagonists & inhibitors*; D000818:Animals; D002460:Cell Line; D047188:Chalcones / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression; D007249:Inflammation / Q000235:genetics / Q000517:prevention & control; D050838:Interferon Regulatory Factor-3; D008213:Lymphocyte Activation; D008264:Macrophages / Q000187:drug effects*; D051379:Mice; D016328:NF-kappa B; D015398:Signal Transduction / Q000187:drug effects*; D051193:Toll-Like Receptors / Q000037:antagonists & inhibitors*
D033942:Adaptor Proteins, Vesicular Transport; D047188:Chalcones; D004791:Enzyme Inhibitors; D050838:Interferon Regulatory Factor-3; D016328:NF-kappa B; D051193:Toll-Like Receptors; C476286:Ticam1 protein, mouse; C040920:isoliquiritigenin