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

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Abstract
Summary. 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 72–96h of culture. Consistently, the analysis of the steady-state levels of mRNA showed a sharp increse of IL-6 mRNA expression after 24h of culture, with a slow decline thereafter. On the other hand, TGF-β1 mRNA expression showed a slow increase only after 72–96h 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-β production both directly and indirectly, through early IL-6 production, could have important implications in the pathogenesis of HIV-1 disease.