Pentoxifylline reduces tumor necrosis factor-α and HIV-induced vascular endothelial activation

Linden Ann Green, Chul Kim, Samir K. Gupta, Gangaraju Rajashekhar, Jalees Rehman, Matthias Clauss

Research output: Contribution to journalReview article

14 Scopus citations

Abstract

Untreated HIV infection is associated with endothelial dysfunction and subsequent cardiovascular disease, likely due to both direct effects of the virus and to indirect effects of systemic inflammation on the vasculature. We have recently shown that treatment with the antiinflammatory agent pentoxifylline (PTX) improved in vivo endothelial function and reduced circulating levels of the inflammatory markers vascular cell adhesion molecule-1 (VCAM-1) and interferon-gamma-induced protein (IP-10) in HIV-infected patients. To delineate the mechanisms underlying this therapeutic effect, we tested whether clinically relevant concentrations of PTX suppress VCAM-1 or IP-10 release in cultivated human lung microvascular endothelial cells. Indeed, we found that tumor necrosis factor (TNF)-α-induced VCAM-1 was reduced with concentrations of PTX in the low nanomolar range, comparable to plasma levels in PTX-treated groups. We also investigated the effect of HIV proteins and found that HIV transactivator of transcription (HIV-Tat) and HIV-envelope-derived recombinant gp120 enhanced TNF-α-induced VCAM-1 gene expression in lung microvascular and coronary macrovascular endothelial cells, respectively. In addition, PTX and a NF-κB-specific inhibitor reduced this enhanced VCAM-1 gene induction in microvascular and macrovascular endothelial cells. These results provide novel insights in how the antiinflammatory agent PTX can directly reduce HIV-associated proinflammatory endothelial activation, which may underlie vascular dysfunction and coronary vascular diseases.

Original languageEnglish (US)
Pages (from-to)1207-1215
Number of pages9
JournalAIDS Research and Human Retroviruses
Volume28
Issue number10
DOIs
StatePublished - Oct 1 2012

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Infectious Diseases

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