TY - JOUR
T1 - Tumor necrosis factor α functions in an autocrine manner in the induction of human immunodeficiency virus expression
AU - Poli, Guido
AU - Kinter, Audrey
AU - Justement, Jesse S.
AU - Kehrl, John H.
AU - Bressler, Peter
AU - Stanley, Sharilyn
AU - Fauci, Anthony S.
PY - 1990
Y1 - 1990
N2 - Tumor necrosis factor α (TNF-α) is an immunoregulatory cytokine capable of inducing viral expression in cells chronically infected with the human immunodeficiency virus (HIV), such as the promonocytic line U1 and the T-lymphocytic line ACH-2. In the present study, we demonstrate an autocrine mechanism of TNF-α-mediated HIV induction. Stimulation of U1 and ACH-2 cells with phorbol 12-myristate 13-acetate (PMA) resulted in the induction of TNF-α mRNA and the secretion of TNF-α. Of note is the fact that anti-TNF-α antibodies significantly suppressed the expression of HIV in PMA-stimulated U1 and ACH-2 cells. Furthermore, anti-TNF-α antibodies also suppressed both the constitutive and inducible levels of viral expression in the chronically infected promonocytic clone U33.3. This study illustrates the interrelationship between the regulation of HIV expression and normal immunoregulatory mechanisms in that virus expression, both constitutive and induced, can be modulated by an autocrine pathway involving TNF-α, a cytokine involved in the complex network of regulation of the normal human immune response.
AB - Tumor necrosis factor α (TNF-α) is an immunoregulatory cytokine capable of inducing viral expression in cells chronically infected with the human immunodeficiency virus (HIV), such as the promonocytic line U1 and the T-lymphocytic line ACH-2. In the present study, we demonstrate an autocrine mechanism of TNF-α-mediated HIV induction. Stimulation of U1 and ACH-2 cells with phorbol 12-myristate 13-acetate (PMA) resulted in the induction of TNF-α mRNA and the secretion of TNF-α. Of note is the fact that anti-TNF-α antibodies significantly suppressed the expression of HIV in PMA-stimulated U1 and ACH-2 cells. Furthermore, anti-TNF-α antibodies also suppressed both the constitutive and inducible levels of viral expression in the chronically infected promonocytic clone U33.3. This study illustrates the interrelationship between the regulation of HIV expression and normal immunoregulatory mechanisms in that virus expression, both constitutive and induced, can be modulated by an autocrine pathway involving TNF-α, a cytokine involved in the complex network of regulation of the normal human immune response.
KW - Phorbol 12-myristate 13-acetate
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M3 - Article
C2 - 2300561
AN - SCOPUS:0025012838
VL - 87
SP - 782
EP - 785
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 2
ER -