title: beta-Carboline alkaloid suppresses NF-kappaB transcriptional activity through inhibition of IKK signaling pathway.
abstract: Nuclear factor (NF)-kappaB transcription factors play an evolutionarily conserved and critical role in the triggering and coordination of both innate and adaptive immune responses. Therefore, there is intense interest in understanding the regulation of this transcription factor in the context of various diseases. Studies investigated the suppression mechanism of NF-kappaB signaling pathways by a beta-carboline alkaloid (C-1) in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. beta-Carboline alkaloid decreased the level of inducible nitric oxide sythase (iNOS) protein and NOS promoter activities in a concentration-dependent manner. This effect was accompanied by the reduction of NF-kappaB DNA binding activity as well as NF-kappaB nuclear translocation. In addition, beta-carboline alkaloid reduced the degradation and phosphorylation of IkappaB, and attenuated IKK activity in LPS-stimulated RAW 264.7 cells. Taken together, these results indicate that beta-carboline alkaloid has the capability to suppress NF-kappaB signaling pathway through inhibition of IKK activity in LPS-stimulated RAW 264.7 cells.
authors.affiliation: College of Pharmacy, Sungkyunkwan University, Changan-gu, Suwon, Korea.
authors.forename: Jong Woo
authors.initials: JW
authors.lastname: Yoon
authors.forename: Jae Ku
authors.initials: JK
authors.lastname: Kang
authors.forename: Kang Ro
authors.initials: KR
authors.lastname: Lee
authors.forename: Hyang Woo
authors.initials: HW
authors.lastname: Lee
authors.forename: Jeung Whan
authors.initials: JW
authors.lastname: Han
authors.forename: Dong Wan
authors.initials: DW
authors.lastname: Seo
authors.forename: Yong Kee
authors.initials: YK
authors.lastname: Kim
mesh_terms: D000470:Alkaloids / Q000633:toxicity*; D000818:Animals; D002243:Carbolines / Q000633:toxicity*; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter; D051550:I-kappa B Kinase / Q000378:metabolism*; D008070:Lipopolysaccharides; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D011401:Promoter Regions, Genetic; D015398:Signal Transduction
chemical_list: C121891:4,8-dimethoxy-1-vinylcarboline; D000470:Alkaloids; D002243:Carbolines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D004247:DNA; D008156:Luciferases; D052247:Nitric Oxide Synthase Type II; D015500:Chloramphenicol O-Acetyltransferase; D051550:I-kappa B Kinase