Interleukin-10-induced HIV-1 expression is mediated by induction of both membrane-bound tumour necrosis factor (TNF)-α and TNF receptor type 1 in a promonocytic cell line

Wilma Barcellini, Gian Paolo Rizzardi, J. Blake Marriott, Cristina Fain, Robin J. Shattock, Pier Luigi Meroni, Guido Poli, Angus G. Dalgleish

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: To investigate whether the upregulatory effect of interleukin (IL)-10 on HIV expression in a model of latent HIV infection is mediated by induction of endogenous tumour necrosis factor (TNF)-α and TNF receptors (TNFR). Design: The latently HIV-infected promonocytic cell line U1 was examined, because in this in vitro model IL-10 has been shown to synergize with multiple cytokines, including TNF-α, in enhancing HIV production. Methods: Membrane-bound TNF-α, TNFR-1 and TNFR-2 surface expression were determined by flow cytometry. TNF-α mRNA was estimated by competitive polymerase chain reaction (PCR), and TNF-α, soluble TNFR-1 and soluble TNFR-2 supernatant content by enzyme-linked immunosorbent assay. HIV-1 expression was quantitated by reverse transcriptase assay and p24 antigen release. Results: We demonstrated that IL-10 induces a time and cell-concentration dependent upregulation of HIV expression in U1 cells. This effect is mediated through the endogenous production of TNF-α as demonstrated by blocking experiments with anti-TNF-α antibodies and by detection of IL-10-induced increase of TNF-α mRNA by competitive PCR. More importantly, IL-10 is able to upregulate membrane-bound TNF-α and TNFR-1, along with a consistent increase in the shedding of soluble TNFR-1 without inducing detectable TNF-α secretion. Conclusions: IL-10 activates HIV expression through the membrane-bound TNF-α TNFR-1 pathway, suggesting an amplification mechanism of HIV expression that might occur during cell-to-cell interaction. This positive regulatory effect of IL-10 in an in vitro model of chronic HIV infection is consistent with the inexorable progression of disease seen in advanced patients when both IL-10 and TNF-α are elevated.

Original languageEnglish
Pages (from-to)835-842
Number of pages8
JournalAIDS (London, England)
Volume10
Issue number8
Publication statusPublished - 1996

Keywords

  • Interleukin-10
  • Latent/inducible HIV infection
  • Membrane-bound TNF-α
  • Promonocytic cell line U1
  • TNF receptors
  • Tumour necrosis factor (TNF)-α

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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