Title |
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
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Published in |
Pflügers Archiv - European Journal of Physiology, February 1999
|
DOI | 10.1007/s004240050815 |
Pubmed ID | |
Authors |
Maria Barcova, Cornelia Speth, Laco Kacani, Florian Überall, Heribert Stoiber, M. P. Dierich |
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-kappaB 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-kappaB binding activity in as much as no NF-kappaB bound to the main NF-kappaB-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 p70(S6)-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-kappaB, MAPK, or PI 3-kinase activation, but rather may operate through activation of adenylate cyclase and pertussis-toxin-sensitive Gi/Go protein to effect p70(S6)-kinase activation. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 10 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 4 | 40% |
Student > Ph. D. Student | 2 | 20% |
Student > Bachelor | 1 | 10% |
Other | 1 | 10% |
Unknown | 2 | 20% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 3 | 30% |
Nursing and Health Professions | 2 | 20% |
Biochemistry, Genetics and Molecular Biology | 1 | 10% |
Immunology and Microbiology | 1 | 10% |
Medicine and Dentistry | 1 | 10% |
Other | 0 | 0% |
Unknown | 2 | 20% |