TY - JOUR
T1 - Activation of signal transduction and apoptosis in healthy lymphomonocytes exposed to bystander HIV-1-infected cells
AU - Abbate, I.
AU - Dianzani, F.
AU - Capobianchi, M. R.
PY - 2000
Y1 - 2000
N2 - Persistent activation of the immune system is one of the hallmarks of HIV-1 infection. In this study we analysed the induction of factors involved in cytokine signal transduction, such as STAT 1 proteins and IRF-1 mRNA, in normal peripheral blood mononuclear cells (PBMC) exposed to HIV-infected cells, and the induction of apoptosis. Western blot analyses and reverse transcriptase-polymerase chain reaction results indicate that both cells infected with a X4 strain and cells infected with a R5 strain are able to increase intracellular levels of STAT 1α and β proteins as well as IRF-1 mRNA. This effect was prevented by neutralizing antibodies against interferon-alpha (IFN-α). HIV-1-infected cells dose-dependently induced apoptotic commitment in normal PBMC, as revealed by DNA fragmentation analysis, but this was not accompanied by an increase of caspase-3 activity, even if a slight up-regulation of IL-1β-converting enzyme mRNA was detected. Apoptosis induction could be abrogated mainly by antibodies against tumour necrosis factor-alpha (TNF-α) and, to a lesser extent, by antibodies against IFN-γ. All these findings suggest that uninfected PBMC can undergo activation of signal transduction and apoptosis after exposure to bystander HIV-infected cells, subsequent to the induction of cytokines such as IFNs and TNF-α.
AB - Persistent activation of the immune system is one of the hallmarks of HIV-1 infection. In this study we analysed the induction of factors involved in cytokine signal transduction, such as STAT 1 proteins and IRF-1 mRNA, in normal peripheral blood mononuclear cells (PBMC) exposed to HIV-infected cells, and the induction of apoptosis. Western blot analyses and reverse transcriptase-polymerase chain reaction results indicate that both cells infected with a X4 strain and cells infected with a R5 strain are able to increase intracellular levels of STAT 1α and β proteins as well as IRF-1 mRNA. This effect was prevented by neutralizing antibodies against interferon-alpha (IFN-α). HIV-1-infected cells dose-dependently induced apoptotic commitment in normal PBMC, as revealed by DNA fragmentation analysis, but this was not accompanied by an increase of caspase-3 activity, even if a slight up-regulation of IL-1β-converting enzyme mRNA was detected. Apoptosis induction could be abrogated mainly by antibodies against tumour necrosis factor-alpha (TNF-α) and, to a lesser extent, by antibodies against IFN-γ. All these findings suggest that uninfected PBMC can undergo activation of signal transduction and apoptosis after exposure to bystander HIV-infected cells, subsequent to the induction of cytokines such as IFNs and TNF-α.
KW - Apoptosis
KW - Cytokines
KW - HIV-1
KW - Signal transduction
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U2 - 10.1046/j.1365-2249.2000.01378.x
DO - 10.1046/j.1365-2249.2000.01378.x
M3 - Article
C2 - 11122243
AN - SCOPUS:0034532223
VL - 122
SP - 374
EP - 380
JO - Clinical and Experimental Immunology
JF - Clinical and Experimental Immunology
SN - 0009-9104
IS - 3
ER -