Suppression of TRIF-dependent signaling pathway of toll-like receptors by allyl isothiocyanate in RAW 264.7 macrophages.
Toll-like receptors (TLR) play a significant role in the induction of innate immune responses that are essential for host defense against invading microbial pathogens. In general, TLRs have two major downstream signaling pathways: myeloid differential factor 88 (MyD88)-dependent and toll-interleukin-1 receptor domain-containing adapter inducing interferon-β (TRIF)-dependent pathways. Allyl isothiocyanate (AITC) found in cruciferous vegetables has an effect on treatment of many chronic diseases. However, the exact molecular targets of AITC are still unidentified. Here, it was investigated whether AITC can modulate TLR signaling pathways and what is the molecular target of AITC in TLRs signaling pathways. AITC suppressed the activation of nuclear factor-κB by lipopolysaccharide (LPS) or polyinosinic-polycytidylic acid (poly[I:C]), but not by macrophage-activating lipopeptide of 2kDa (MALP-2) or cytosine-phosphate-guanine dinucleotide (CpG DNA). AITC also suppressed the activation of interferon regulatory factor 3 (IRF3) and the expression of interferon inducible protein-10 (IP-10) induced by LPS or poly[I:C]. These results suggest that AITC can modulate TRIF-dependent signaling pathways of TLRs leading to decreased inflammatory gene expression.
Department of Biomedical Laboratory Science, College of Medical Sciences, Soonchunhyang University, Asan-Si, Chungnam 336-745, Korea.
Soo-Jung
SJ
Kim
Hye-Jeong
HJ
Park
Hwa-Jeong
HJ
Shin
Dong-Hwa
DH
Shon
Do Hyun
DH
Kim
Hyung-Sun
HS
Youn
D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002460:Cell Line; D054357:Chemokine CXCL10 / Q000378:metabolism; D050838:Interferon Regulatory Factor-3 / Q000235:genetics / Q000378:metabolism; D017879:Isothiocyanates / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D011070:Poly I-C / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D051193:Toll-Like Receptors / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects
D033942:Adaptor Proteins, Vesicular Transport; D000894:Anti-Inflammatory Agents, Non-Steroidal; D054357:Chemokine CXCL10; D050838:Interferon Regulatory Factor-3; D017879:Isothiocyanates; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011070:Poly I-C; D051193:Toll-Like Receptors; C494233:Irf3 protein, mouse; C476286:Ticam1 protein, mouse; C004471:allyl isothiocyanate