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Interleukin‐8 fails to induce human immunodeficiency virus‐1 expression in chronically infected promonocytic U1 cells but differentially modulates induction by proinflammatory cytokines
Author(s) -
Tiemessen C. T.,
Kilroe B.,
Martin D. J.
Publication year - 2000
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.2000.00100.x
Subject(s) - proinflammatory cytokine , cytokine , chemokine , biology , tumor necrosis factor alpha , interleukin , interferon , u937 cell , immunology , cell culture , inflammation , genetics
Summary This study addresses the role of interleukin (IL)‐8, a CXC‐chemokine, the level of which is reported to be raised in the peripheral circulation of human immunodeficiency virus‐1 (HIV‐1)‐infected individuals, during the induction of HIV‐1 expression from latency and during cytokine‐mediated HIV‐1 up‐regulation. IL‐8 at the higher concentrations tested (≥ 100 ng/ml) was unable to induce HIV‐1 expression in the chronically infected promonocytic U1 cell line, as measured by p24 antigen enzyme‐linked immunosorbent assay (ELISA), whereas at lower concentrations of 1 and 10 ng/ml, constitutive HIV‐1 expression was only marginally reduced. HIV‐1 replication in acutely infected U937 cells was also significantly reduced by IL‐8. The potent up‐regulation of HIV‐1 expression in U1 cells by tumour necrosis factor‐α (TNF‐α) remained unaffected by the addition of IL‐8. HIV‐1 induction by IL‐1β, IL‐6 and TNF‐β, cytokines grouped here as intermediate HIV‐1 inducers, was suppressed by IL‐8 at concentrations of 1 and 10 ng/ml. However, IL‐8 at 100 ng/ml did not significantly alter the effect of IL‐1β, synergized with IL‐6 in enhancing, and marginally suppressed TNF‐β‐induced HIV‐1 expression. IL‐8 suppressed granulocyte–macrophage colony‐stimulating factor (GM‐CSF) and enhanced interferon‐γ (IFN‐γ)‐induced HIV‐1 expression in a dose‐dependent manner. Pretreatment of U1 cells with IL‐8 did not alter the IL‐8‐mediated effects on cytokine‐induced HIV‐1 expression, suggesting that this chemokine exerts its effect at the time of HIV‐1 induction or at a postinduction stage. Furthermore, IL‐8 was itself induced by cytokines that up‐regulate HIV‐1 expression in U1 cells and the levels produced correlated directly with the levels of p24 antigen produced, suggesting common pathways for cytokine induction of both HIV‐1 and IL‐8. These results show that IL‐8, typically a non‐inducer, can differentially modulate HIV‐1 expression in U1 cells and that this is dependent on the inducing cytokine and on the concentration of IL‐8.