Recombinant human immunodeficiency virus type-1 (HIV-1) Tat protein sequentially up-regulates IL-6 and TGF-β1 mRNA expression and protein synthesis in peripheral blood monocytes

D. Gibellini, G. Zauli, M. C. Re, D. Milani, G. Furlini, E. Caramelli, S. Capitani, M. La Placa

Research output: Contribution to journalArticlepeer-review

Abstract

In this study we evaluated the effect of human immunodeficiency virus type 1 (HIV-1) recombinant Tat protein on mRNA expression and protein synthesis of two inflammatory cytokines - interleukin-6 (IL-6) and transforming growth factor-β1 (TGF-β1) - by peripheral blood (PB) monocytes. Whereas maximal levels of IL-6 protein were recovered in PB monocyte culture supernatants after 24-48 h from the addition of 1 μg/ml of recombinant Tat, TGF-β1 showed a slower and progressive increase, reaching maximal levels only after 72-96 h of culture. Consistently, the analysis of the steady-state levels of mRNA showed a sharp increase of IL-6 mRNA expression after 24 h of culture, with a slow decline thereafter. On the other hand, TGF-β1 mRNA expression showed a slow increase only after 72-96 h of culture. Moreover, IL-6 appeared involved in the up-regulation of TGF-β1, because the addition of a neutralizing anti-IL-6 antibody to Tat-treated PB monocyte cultures significantly reduced the amounts of TGF-β1 recovered in the culture supernatants after 96 h. The present demonstration that HIV-1 Tat protein directly up-regulates IL-6 expression and stimulates TGF-β1 production both directly and indirectly, through early IL-6 production, could have important implications in the pathogenesis of HIV-1 disease.

Original languageEnglish
Pages (from-to)261-267
Number of pages7
JournalBritish Journal of Haematology
Volume88
Issue number2
Publication statusPublished - 1994

Keywords

  • HIV-1
  • IL-6
  • Tat protein
  • TGF-β1

ASJC Scopus subject areas

  • Hematology

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