beta-Carboline alkaloid suppresses NF-kappaB transcriptional activity through inhibition of IKK signaling pathway.
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.
Yoon
Jong Woo
JW
College of Pharmacy, Sungkyunkwan University, Changan-gu, Suwon, Korea.
Kang
Jae Ku
JK
Lee
Kang Ro
KR
Lee
Hyang Woo
HW
Han
Jeung Whan
JW
Seo
Dong Wan
DW
Kim
Yong Kee
YK
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
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