HIV-1 gp160 induces transforming growth factor-beta production in human PBMC.
Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine secreted by many mononuclear cells in peripheral blood (PBMC) and has diverse effects on cellular and humoral immunity. Increased TGF-beta mRNA expression has been reported in PBMC of HIV-infected patients, but the mechanism by which HIV induces TGF-beta secretion is unknown. In this study, we observed that HIV gp160 could induce significant TGF-beta secretion and TGF-beta mRNA expression in PBMC from HIV-seronegative healthy donors. The cellular source of TGF-beta was attributed to non-T cells, presumably monocytes. Specificity of secreted TGF-beta was confirmed by the addition of anti-TGF-beta mAb which abrogated the proliferative response of CCL-64 cells by gp160-treated culture supernatants. Soluble CD4 blocked the gp160-induced TGF-beta production, suggesting that CD4-gp160 interaction is required to induce TGF-beta production. Our results suggest that HIV-1 gp160 may contribute to the immune defects in HIV infection by inducing TGF-beta secretion.
Hu
R
R
Department of Pediatrics, North Shore University Hospital-Cornell University Medical College, Manhasset, New York 11030, USA.
Oyaizu
N
N
Than
S
S
Kalyanaraman
V S
VS
Wang
X P
XP
Pahwa
S
S
D000906:Antibodies / Q000494:pharmacology; D001483:Base Sequence; D015704:CD4 Antigens / Q000494:pharmacology; D016827:CD8 Antigens / Q000502:physiology; D002240:Carbohydrate Sequence; D002478:Cells, Cultured; D004347:Drug Interactions; D015686:Gene Products, env / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D019302:HIV Envelope Protein gp160; D006801:Humans; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism*; D008969:Molecular Sequence Data; D011498:Protein Precursors / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000276:immunology / Q000378:metabolism
D000906:Antibodies; D015704:CD4 Antigens; D016827:CD8 Antigens; D015686:Gene Products, env; D019302:HIV Envelope Protein gp160; D011498:Protein Precursors; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta