Interleukin 10 is induced by recombinant HIV-1 Nef protein involving the calcium/calmodulin-dependent phosphodiesterase signal transduction pathway.
HIV-1 Nef protein shares a significant homology with the immunosuppressive and highly conserved retroviral transmembrane protein p15E. In the present study, extracellular Nef protein is shown to induce interleukin (IL)-10 mRNA expression in human peripheral blood mononuclear cells as well as in cells of H9 T and U937 promonocytic human cell lines. Release of IL-10 protein into supernatants of peripheral blood mononuclear cells stimulated with Nef is dose-dependent. Expression of cytokines IL-2, IL-4, IL-5, IL-12 p40, IL-13, and interferon gamma is not affected by Nef stimulation. IL-10 protein production induced by Nef is inhibited by the calcium/calmodulin phosphodiesterase inhibitor W-7 but not by the protein kinase A inhibitor H-89 nor the protein kinase C inhibitors staurosporine and calphostin C. The calcium chelating agent EGTA also inhibits the IL-10 production induced by Nef, and this inhibition is reversed by the addition of calcium along with Nef. These findings indicate that extracellular Nef may contribute to the immunopathogenesis of HIV infection by inducing IL-10.
Brigino
E
E
Department of Pediatrics, University of South Florida, St. Petersburg 33701, USA.
Haraguchi
S
S
Koutsonikolis
A
A
Cianciolo
G J
GJ
Owens
U
U
Good
R A
RA
Day
N K
NK
D002460:Cell Line; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; D004533:Egtazic Acid / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation; D015693:Gene Products, nef / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D007546:Isoquinolines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D013449:Sulfonamides; D054311:nef Gene Products, Human Immunodeficiency Virus
D004791:Enzyme Inhibitors; D015693:Gene Products, nef; D007546:Isoquinolines; D009281:Naphthalenes; D012333:RNA, Messenger; D011994:Recombinant Proteins; D013449:Sulfonamides; D054311:nef Gene Products, Human Immunodeficiency Virus; D016753:Interleukin-10; D004533:Egtazic Acid; D010727:Phosphoric Diester Hydrolases; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; C058819:calphostin C; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide