Pflügers Archiv

, Volume 437, Issue 4, pp 538–546

Involvement of adenylate cyclase and p70S6-kinase activation in IL-10 up-regulation in human monocytes by gp41 envelope protein of human immunodeficiency virus type 1

  • Maria Barcova
  • Cornelia Speth
  • Laco Kacani
  • Florian Überall
  • Heribert Stoiber
  • M. P. Dierich
ORIGINAL ARTICLE

DOI: 10.1007/s004240050815

Cite this article as:
Barcova, M., Speth, C., Kacani, L. et al. Pflügers Arch (1999) 437: 538. doi:10.1007/s004240050815

Abstract.

Our previous results show that recombinant gp41 (aa565–647), the extracellular domain of HIV-1 transmembrane glycoprotein, stimulates interleukin-10 (IL-10) production in human monocytes. The signal cascade transducing this effect is not yet clear. In this study, we examined whether gp41-induced IL-10 up-regulation is mediated by the previously described synergistic activation of cAMP and NF-κB pathways. gp41 induced cAMP accumulation in monocytes in a time- and concentration-dependent manner and the adenylate cyclase inhibitor SQ 22536 suppressed gp41-induced IL-10 production in monocytes. In contrast, gp41 failed to stimulate NF-κB binding activity in as much as no NF-κB bound to the main NF-κB-binding site 2 of the IL-10 promoter after addition of gp41. We also examined the involvement of other signal transduction pathways. Specific inhibitors of p70S6-kinase (rapamycin), and Gi protein (pertussis toxin), prevented induction of IL-10 production by gp41 in monocytes, while inhibitors of the phosphatidylinositol 3-kinase (PI 3-kinase) (wortmannin) and mitogen-activated protein kinase (MAPK) pathway (PD 98059) did not. Thus HIV-1 gp41-induced IL-10 up-regulation in monocytes may not involve NF-κB, MAPK, or PI 3-kinase activation, but rather may operate through activation of adenylate cyclase and pertussis-toxin-sensitive Gi/Go protein to effect p70S6-kinase activation.

Key words cAMP gp41 G protein IL-10 NF-κB Peripheral blood mononuclear cells S6 kinase Signal transduction 

Copyright information

© Springer-Verlag Berlin Heidelberg 1999

Authors and Affiliations

  • Maria Barcova
    • 1
  • Cornelia Speth
    • 1
  • Laco Kacani
    • 1
  • Florian Überall
    • 3
  • Heribert Stoiber
    • 1
  • M. P. Dierich
    • 1
  1. 1.Institute for Hygiene, University of Innsbruck, Fritz-Pregl-Str. 3, A-6020 Innsbruck, Austria e-mail: hygiene@uibk.ac.at Tel.: +43-512-5073401 Fax: +43-512-5072870AT
  2. 2.Ludwig Boltzmann-Institute for AIDS Research, Innsbruck, AustriaAT
  3. 3.Institute for Medical Chemistry and Biochemistry, Innsbruck, AustriaAT

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