title: Imperatorin inhibits T-cell proliferation by targeting the transcription factor NFAT.
abstract: In our ongoing research into anti-inflammatory compounds from medicinal plants in the Mediterranean area, we have isolated several furanocoumarins from the roots of Oppopanax chironium (L.), and have evaluated them for activity related to T-cell functionality. Heraclenin (1) and imperatorin (2) significantly inhibited T cell receptor-mediated proliferation in human primary T cells in a concentration-dependent manner. In transient transfection experiments with a plasmid containing the IL-2 promoter we found that imperatorin is a potent inhibitor of IL-2 gene transcription. To further characterize the inhibitory mechanisms of imperatorin at the transcriptional level, we examined the DNA-binding and transcriptional activities of NF-kappaB, NFAT, and AP-1 transcription factors in Jurkat T cells. We found that imperatorin inhibited both the NFAT binding to DNA and transcriptional activities, without affecting significantly the activation of the NF-kappaB and AP-1 transcription factors. These findings provide new insights into the molecular mechanisms involved in the immunomodulatory and anti-inflammatory activities of natural furanocoumarins.
authors.affiliation: Departamento de Biología Celular, Fisiología e Inmunología, Universidad de Córdoba, Facultad de Medicina, Córdoba, Spain.
authors.forename: Nieves
authors.initials: N
authors.lastname: Márquez
authors.forename: Rocío
authors.initials: R
authors.lastname: Sancho
authors.forename: Mauro
authors.initials: M
authors.lastname: Ballero
authors.forename: Paul
authors.initials: P
authors.lastname: Bremner
authors.forename: Giovanni
authors.initials: G
authors.lastname: Appendino
authors.forename: Bernd L
authors.initials: BL
authors.lastname: Fiebich
authors.forename: Michael
authors.initials: M
authors.lastname: Heinrich
authors.forename: Eduardo
authors.initials: E
authors.lastname: Muñoz
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D019661:Apiaceae; D049109:Cell Proliferation / Q000187:drug effects*; D004268:DNA-Binding Proteins / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D011564:Furocoumarins / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D019169:Jurkat Cells / Q000187:drug effects; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins / Q000187:drug effects*; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D018517:Plant Roots; D013601:T-Lymphocytes / Q000187:drug effects*; D014157:Transcription Factors / Q000187:drug effects*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004268:DNA-Binding Proteins; D011564:Furocoumarins; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D010936:Plant Extracts; D014157:Transcription Factors; C031534:imperatorin