Activation of cytokine genes in HIV-1 infected myelomonoblastic cells by phorbol ester and tumor necrosis factor.
The differential production of inflammatory cytokines (IL-1 alpha, IL-1 beta, IL-6, and TNF-alpha) was analyzed in the PLB-985 myelomonoblastic cell line, chronically infected or not by the IIIB strain of HIV-1. After treatment with phorbol ester (PMA) or TNF-alpha, a 20- to 40-fold increase in the level of IL-1 beta mRNA was observed in the HIV-infected PLB-IIIB as compared with the parental PLB-985 cells. The majority of the IL-1 beta activity detected in both cell types remained cell associated. In contrast, TNF-alpha mRNA levels were increased in both infected and uninfected cells; the t1/2 of TNF RNA was 90 min in uninfected cells and 30 min in HIV-infected cells. Interestingly, about 14-fold more TNF activity was secreted from PLB-IIIB than from similarly stimulated PLB-985 cells, indicating an enhanced translational efficiency of TNF RNA in PLB-IIIB cells. The PMA- or TNF-induced levels of IL-1 alpha mRNA did not vary significantly between the two cell types whereas IL-6 was poorly inducible in both cells. These results illustrate a differential cytokine response to HIV-1 infection in myeloid cells and demonstrate that HIV-1 infection of myelomonoblastic cells may alter both transcriptional and translational mechanisms controlling cytokine expression.
Lady Davis Institute, Sir Mortimer B Davis-Jewish General Hospital, Montreal, Quebec, Canada.
M
M
D'Addario
M A
MA
Wainberg
J
J
Hiscott
D001483:Base Sequence; D001853:Bone Marrow / Q000276:immunology; D002460:Cell Line; D016207:Cytokines / Q000235:genetics*; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000235:genetics*; D015497:HIV-1; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D012313:RNA / Q000032:analysis; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000494:pharmacology*
D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D012313:RNA; D013755:Tetradecanoylphorbol Acetate