Retinoic acid inhibits IL-6-dependent but not constitutive STAT3 activation in Epstein-Barr virus-immortalized B lymphocytes

  • Authors:
    • Paola Zancai
    • Roberta Cariati
    • Michele Quaia
    • Massimo Guidoboni
    • Silvana Rizzo
    • Mauro Boiocchi
    • Riccardo Dolcetti
  • View Affiliations

  • Published online on: August 1, 2004     https://doi.org/10.3892/ijo.25.2.345
  • Pages: 345-355
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Abstract

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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August 2004
Volume 25 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Zancai P, Cariati R, Quaia M, Guidoboni M, Rizzo S, Boiocchi M and Dolcetti R: Retinoic acid inhibits IL-6-dependent but not constitutive STAT3 activation in Epstein-Barr virus-immortalized B lymphocytes. Int J Oncol 25: 345-355, 2004.
APA
Zancai, P., Cariati, R., Quaia, M., Guidoboni, M., Rizzo, S., Boiocchi, M., & Dolcetti, R. (2004). Retinoic acid inhibits IL-6-dependent but not constitutive STAT3 activation in Epstein-Barr virus-immortalized B lymphocytes. International Journal of Oncology, 25, 345-355. https://doi.org/10.3892/ijo.25.2.345
MLA
Zancai, P., Cariati, R., Quaia, M., Guidoboni, M., Rizzo, S., Boiocchi, M., Dolcetti, R."Retinoic acid inhibits IL-6-dependent but not constitutive STAT3 activation in Epstein-Barr virus-immortalized B lymphocytes". International Journal of Oncology 25.2 (2004): 345-355.
Chicago
Zancai, P., Cariati, R., Quaia, M., Guidoboni, M., Rizzo, S., Boiocchi, M., Dolcetti, R."Retinoic acid inhibits IL-6-dependent but not constitutive STAT3 activation in Epstein-Barr virus-immortalized B lymphocytes". International Journal of Oncology 25, no. 2 (2004): 345-355. https://doi.org/10.3892/ijo.25.2.345