Your browser doesn't support javascript.
loading
Retinoic acid inhibits IL-6-dependent but not constitutive STAT3 activation in Epstein-Barr virus-immortalized B lymphocytes.
Zancai, Paola; Cariati, Roberta; Quaia, Michele; Guidoboni, Massimo; Rizzo, Silvana; Boiocchi, Mauro; Dolcetti, Riccardo.
Afiliação
  • Zancai P; Immunovirology and Biotherapy Unit, Department of Pre-clinical and Epidemiological Research, Centro di Riferimento Oncologico, IRCCS - National Cancer Institute, Aviano (PN), Italy.
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.
Assuntos
Buscar no Google
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
Buscar no Google
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