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Titolo:
The T-cell suppressive effect of bufadienolides: structural requirements for their immunoregulatory activity
Autore:
Terness, P; Navolan, D; Dufter, C; Kopp, B; Opelz, G;
Indirizzi:
Univ Heidelberg, Inst Immunol, Dept Transplantat Immunol, INF 305, D-69120Heidelberg, Germany Univ Heidelberg Heidelberg Germany D-69120 5, D-69120Heidelberg, Germany Minist Hlth, Bucharest, Romania Minist Hlth Bucharest RomaniaMinist Hlth, Bucharest, Romania Univ Vienna, Inst Pharmacognosy, Vienna, Austria Univ Vienna Vienna Austria Vienna, Inst Pharmacognosy, Vienna, Austria
Titolo Testata:
INTERNATIONAL IMMUNOPHARMACOLOGY
fascicolo: 1, volume: 1, anno: 2001,
pagine: 119 - 134
SICI:
1567-5769(200101)1:1<119:TTSEOB>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
DIGITALIS-LIKE FACTORS; OUABAIN-LIKE COMPOUND; HUMAN TUMOR-CELLS; MARINOBUFAGENIN-LIKE; SODIUM-PUMP; DIABETES-MELLITUS; VOLUME EXPANSION; BOVINE ADRENALS; BLOOD-PRESSURE; IN-VITRO;
Keywords:
human T lymphocytes; suppression; immunomodulators; cardiac steroids; bufadienolides;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
49
Recensione:
Indirizzi per estratti:
Indirizzo: Terness, P Univ Heidelberg, Inst Immunol, Dept Transplantat Immunol, INF 305, Neuenheimer Feld 230, D-69120 Heidelberg, Germany Univ Heidelberg Neuenheimer Feld 230 Heidelberg Germany D-69120
Citazione:
P. Terness et al., "The T-cell suppressive effect of bufadienolides: structural requirements for their immunoregulatory activity", INT IMMUNO, 1(1), 2001, pp. 119-134

Abstract

Many studies indicate that substances similar to cardenolides and bufadienolides naturally occur in mammals. The majority of previous studies focusedon their cardiovascular, renal, and central nervous action. We analyzed the immunoregulatory property of 52 bufadienolides. I Human T-cells were stimulated "in vitro" with mitogens or alloantigens in the presence of bufadienolides. The most active compound totally inhibited T-cell activity at a concentration of 0.75 pmol/10(5) cells. This effect is 16 384 x stronger than that of cortisol and 256 X stronger than that of cyclosporin A or tacrolimus. Preactivated T cells were downregulated and, most importantly, suppressed viable T cells could not be restimulated. Lack of the 17 beta -lactone ring dramatically reduced the activity of bufadienolides. Substitution at C3 also affected their function: components with a 3-OH group were up to 1000 X stronger than those without. The replacement of 14P-OII with an epoxy-group slightly decreased the activity. Because there is evidence that the latter change abolishes the cardiac activity, this finding is relevant for therapeutic applications in which immunosuppression without the risk of cardiotoxicity is attempted. One of the substances analyzed in this study was Proscillaridin A. A similar bufadienolide occurs naturally in mammals. We speculate that bufadienolides represent an important bioregulatory link between the cardiovascular, nervous and immune systetns. (C) 2001 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 09/04/20 alle ore 10:50:30