Podophyllotoxin and α-peltatin inhibit nuclear factor κB activation and gene expression stimulated by a double-stranded RNA analogue in human umbilical vein endothelial cells.
{"title":"Podophyllotoxin and α-peltatin inhibit nuclear factor κB activation and gene expression stimulated by a double-stranded RNA analogue in human umbilical vein endothelial cells.","authors":"Yuka Yokota, Piimwara Yarangsee, Kosuke Baba, Saki Sasaki, Hiroyuki Hirano, Hiroyuki Osada, Takao Kataoka","doi":"10.1093/bbb/zbaf108","DOIUrl":null,"url":null,"abstract":"<p><p>In vascular endothelial cells, proinflammatory cytokines and Toll-like receptor (TLR) ligands up-regulate the expression of adhesion molecules. In the present study, screening of the RIKEN Natural Products Depository chemical libraries identified podophyllotoxin and α-peltatin, which inhibited intercellular adhesion molecule-1 (ICAM-1) expression induced by polyinosinic-polycytidylic acid (Poly(I:C)) as a TLR3 ligand. In human umbilical vein endothelial cells (HUVEC), podophyllotoxin and its derivative α-peltatin inhibited Poly(I:C)-induced increases in the mRNA expression of ICAM-1, vascular cell adhesion molecule-1 (VCAM-1), and E-selectin. In addition, podophyllotoxin and α-peltatin inhibited the Poly(I:C)-induced nuclear translocation of the nuclear factor κB (NF-κB) subunit RelA. Microtubule-targeting agents (colchicine, vinblastine, and paclitaxel) exerted different effects on the Poly(I:C)-induced mRNA expression of ICAM-1, VCAM-1, and E-selectin. Vinblastine potently inhibited nuclear RelA translocation in Poly(I:C)-stimulated HUVEC, whereas colchicine and paclitaxel did not. Collectively, these results demonstrate that podophyllotoxin and α-peltatin inhibited NF-κB activation and mRNA expression by TLR3 stimulation in HUVEC.</p>","PeriodicalId":9175,"journal":{"name":"Bioscience, Biotechnology, and Biochemistry","volume":" ","pages":"1432-1443"},"PeriodicalIF":1.3000,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Bioscience, Biotechnology, and Biochemistry","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1093/bbb/zbaf108","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
In vascular endothelial cells, proinflammatory cytokines and Toll-like receptor (TLR) ligands up-regulate the expression of adhesion molecules. In the present study, screening of the RIKEN Natural Products Depository chemical libraries identified podophyllotoxin and α-peltatin, which inhibited intercellular adhesion molecule-1 (ICAM-1) expression induced by polyinosinic-polycytidylic acid (Poly(I:C)) as a TLR3 ligand. In human umbilical vein endothelial cells (HUVEC), podophyllotoxin and its derivative α-peltatin inhibited Poly(I:C)-induced increases in the mRNA expression of ICAM-1, vascular cell adhesion molecule-1 (VCAM-1), and E-selectin. In addition, podophyllotoxin and α-peltatin inhibited the Poly(I:C)-induced nuclear translocation of the nuclear factor κB (NF-κB) subunit RelA. Microtubule-targeting agents (colchicine, vinblastine, and paclitaxel) exerted different effects on the Poly(I:C)-induced mRNA expression of ICAM-1, VCAM-1, and E-selectin. Vinblastine potently inhibited nuclear RelA translocation in Poly(I:C)-stimulated HUVEC, whereas colchicine and paclitaxel did not. Collectively, these results demonstrate that podophyllotoxin and α-peltatin inhibited NF-κB activation and mRNA expression by TLR3 stimulation in HUVEC.
期刊介绍:
Bioscience, Biotechnology, and Biochemistry publishes high-quality papers providing chemical and biological analyses of vital phenomena exhibited by animals, plants, and microorganisms, the chemical structures and functions of their products, and related matters. The Journal plays a major role in communicating to a global audience outstanding basic and applied research in all fields subsumed by the Japan Society for Bioscience, Biotechnology, and Agrochemistry (JSBBA).