Hyperforin down-regulates effector function of activated T lymphocytes and shows efficacy against Th1-triggered CNS inflammatory-demyelinating disease.
Hyperforin (Hyp) is an active compound contained in the extract of Hypericum perforatum, well known for its antidepressant activity. However, Hyp has been found to possess several other biological properties, including inhibitory effects on tumor invasion, angiogenesis, and inflammation. In this paper, we show that treatment with Hyp inhibited IFN-gamma production, with down-regulation of T-box (T-bet; marker of Th1 gene expression) and up-regulation of GATA-3 (marker gene of Th2) on IL-2/PHA-activated T cells. In parallel, we showed a strong down-regulation of the chemokine receptor CXCR3 expression on activated T cells. The latter effect and the down-modulation of matrix metalloproteinase 9 expression may eventually lead to the inhibition of migratory capability and matrix traversal toward the chemoattractant CXCL10 by activated lymphocytes that we observed in vitro. The effect of Hyp was thus evaluated on an animal model of experimental allergic encephalomyelitis (EAE), a classic, Th1-mediated autoimmune disease of the CNS, and we observed that Hyp attenuates the severity of the disease symptoms significantly. Together, these properties qualify Hyp as a putative, therapeutic molecule for the treatment of autoimmune inflammatory disease sustained by Th1 cells, including EAE.
Cabrelle
Anna
A
Department of Clinical and Experiment Medicine, Medical School, Padova, Italy.
Dell'Aica
Isabella
I
Melchiori
Luca
L
Carraro
Samuela
S
Brunetta
Enrico
E
Niero
Raffaele
R
Scquizzato
Elisa
E
D'Intino
Giulia
G
Calzà
Laura
L
Garbisa
Spiridione
S
Agostini
Carlo
C
D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology / Q000627:therapeutic use; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D050990:GATA3 Transcription Factor / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology; D007376:Interleukin-2 / Q000494:pharmacology; D010696:Phloroglucinol / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D010835:Phytohemagglutinins / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D054367:Receptors, CXCR3 / Q000096:biosynthesis / Q000187:drug effects; D020825:T-Box Domain Proteins / Q000187:drug effects / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D013729:Terpenes / Q000494:pharmacology* / Q000627:therapeutic use; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
D001643:Bridged Bicyclo Compounds; C515187:CXCR3 protein, human; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D007376:Interleukin-2; D010835:Phytohemagglutinins; D054367:Receptors, CXCR3; D020825:T-Box Domain Proteins; D013729:Terpenes; D007371:Interferon-gamma; D010696:Phloroglucinol; C001654:hyperforin