title: Suppression of the TRIF-dependent signaling pathway of Toll-like receptor by CDr10b in RAW264.7 macrophages.
abstract: Toll-like receptors (TLRs) recognize distinct pathogen-associated molecular patterns and play a critical role in innate immune responses. TLR signaling pathways can be largely classified as either myeloid differential factor 88 (MyD88)- or toll-interleukin-1 receptor domain-containing adapter inducing interferon-β (TRIF)-dependent pathways. Compound of Designation red 10 binding (CDr10b) was synthesized to investigate its role in neuroinflammatory diseases. This study was conducted to determine whether CDr10b can affect TLR signaling pathways. CDr10b suppressed NF-κB activation as well as COX-2 and iNOS expression induced by TLR3 or TLR4 agonists. CDr10b also suppressed the activation of interferon regulatory factor 3 (IRF3) and the expression of interferon inducible protein-10 (IP-10) induced by TLR3 or TLR4 agonists. These results indicate that CDr10b can modulate the TRIF-dependent pathway of TLRs and has the potential to become a new therapeutic drug for chronic inflammatory diseases.
authors.affiliation: Departments of Medical Science, College of Medical Sciences, SoonChunHyang University, Chungnam, Asan 336-745, Republic of Korea.
authors.forename: Gyo-Jeong
authors.initials: GJ
authors.lastname: Gu
authors.affiliation: Departments of Medical Science, College of Medical Sciences, SoonChunHyang University, Chungnam, Asan 336-745, Republic of Korea.
authors.forename: Sang-Il
authors.initials: SI
authors.lastname: Ahn
authors.affiliation: Departments of Medical Science, College of Medical Sciences, SoonChunHyang University, Chungnam, Asan 336-745, Republic of Korea.
authors.forename: Ji-Soo
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Department of Biomedical Laboratory Science, College of Medical Sciences, SoonChunHyang University, Chungnam, Asan 336-745, Republic of Korea.
authors.forename: Chae-Yeon
authors.initials: CY
authors.lastname: Hong
authors.affiliation: Aptabio Therapeutics Inc., Kyunggi-do, Yong-in city 446-908, Republic of Korea.
authors.forename: Sung-Chan
authors.initials: SC
authors.lastname: Lee
authors.affiliation: Department of Chemistry and MedChem Program, Life Sciences Institute, National University of Singapore, 3 Science Drive 3, Singapore, 117543; Laboratory of Bioimaging Probe Development, Singapore Bioimaging Consortium (SBIC), 11 Biopolis Way, #02-02 Helios, Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore, 138667.
authors.forename: Young-Tae
authors.initials: YT
authors.lastname: Chang
authors.affiliation: Department of Imaging, Korea Institute of Radiological & Medical Sciences, Seoul 139-706, Republic of Korea.
authors.forename: Tae Hyun
authors.initials: TH
authors.lastname: Choi
authors.affiliation: Department of Imaging, Korea Institute of Radiological & Medical Sciences, Seoul 139-706, Republic of Korea.
authors.forename: Byoung Soo
authors.initials: BS
authors.lastname: Kim
authors.affiliation: Departments of Medical Science, College of Medical Sciences, SoonChunHyang University, Chungnam, Asan 336-745, Republic of Korea; Department of Biomedical Laboratory Science, College of Medical Sciences, SoonChunHyang University, Chungnam, Asan 336-745, Republic of Korea. Electronic address: hyoun@sch.ac.kr.
authors.forename: Hyung-Sun
authors.initials: HS
authors.lastname: Youn
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000187:drug effects*; D000818:Animals; D001896:Boron Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D054357:Chemokine CXCL10 / Q000096:biosynthesis; D051546:Cyclooxygenase 2 / Q000187:drug effects; D050838:Interferon Regulatory Factor-3 / Q000096:biosynthesis / Q000235:genetics; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D016328:NF-kappa B / Q000187:drug effects; D052247:Nitric Oxide Synthase Type II / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics; D000067996:RAW 264.7 Cells; D015398:Signal Transduction / Q000187:drug effects; D051196:Toll-Like Receptor 3 / Q000819:agonists; D051197:Toll-Like Receptor 4 / Q000819:agonists; D051193:Toll-Like Receptors / Q000037:antagonists & inhibitors*
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D001896:Boron Compounds; D054357:Chemokine CXCL10; D051546:Cyclooxygenase 2; D050838:Interferon Regulatory Factor-3; D016328:NF-kappa B; D052247:Nitric Oxide Synthase Type II; D017346:Protein Serine-Threonine Kinases; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; C000591023:CDr10b compound; C485433:Cxcl10 protein, mouse; C476286:Ticam1 protein, mouse; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; C498588:Tbk1 protein, mouse
keywords: CDr10b; IP-10; IRF3; TRIF; Toll-like receptor