Retinoic acid inhibits IL-6-dependent but not constitutive STAT3 activation in Epstein-Barr virus-immortalized B lymphocytes.
Int J Oncol
; 25(2): 345-55, 2004 Aug.
Article
em En
| MEDLINE
| ID: mdl-15254731
IL-6-mediated B-cell growth promotion is involved in the pathogenesis of EBV+ lymphoproliferative disorders of immunosuppressed patients. Since retinoic acid (RA) inhibits the proliferation of EBV-immortalized lymphoblastoid B-cell lines (LCLs), we have investigated the effects of RA on IL-6 signaling in these cells. RA down-regulated IL-6-receptor components with IL-6 agonist activity (membrane and soluble gp80) and increased the levels of soluble gp130, an IL-6 antagonist. These changes, however, were not related to the enhanced production of endogenous IL-6 induced by RA in LCLs. RA-induced modulation of IL-6 receptor components did not abolish IL-6-mediated phosphorylation of gp130, whereas JAK1 and STAT3 phosphorylation and activation induced by IL-6 were markedly inhibited. Overall, the effects of RA resulted in the induction of a complete resistance of LCLs to IL-6-mediated growth promotion. Conversely, RA did not inhibit the constitutive activation of JAK1, TYK2, STAT3 and ERK1/2, ruling out that the JAK/STAT and MAPK pathways may mediate the antiproliferative activity of RA. The finding that RA severely impairs IL-6-dependent signalings in LCLs and inhibits their growth despite the presence of constitutively active JAK/STAT and MAPK cascades provide additional support for a role of RA in the prevention and treatment of EBV-related lymphoproliferative disorders of immunosuppressed patients.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tretinoína
/
Linfócitos B
/
Transativadores
/
Interleucina-6
/
Herpesvirus Humano 4
/
Receptores de Interleucina-6
/
Proteínas de Ligação a DNA
Limite:
Humans
Idioma:
En
Revista:
Int J Oncol
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2004
Tipo de documento:
Article
País de afiliação:
Itália