Inhibition of CD4 cross-linking - Induced lymphocytes apoptosis by vesnarinone as a novel immunomodulating agent: Vesnarinone inhibits fas expression and apoptosis by blocking cytokine secretion

Naoki Oyaizu, Thomas W. Mc Closkey, Soe Than, Savita Pahwa

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Evidence is accumulating that T cells from human immunodeficiency virus type 1 (HIV-1)-infected individuals show accelerated cell death through apoptosis. We have recently demonstrated that the cross-linking of CD4 molecules (CD4XL) results in death of normal peripheral T cells through apoptosis and imbalanced cytokine secretion (ie, induction of tumor necrosis factor-α [TNF-α] and interferon-γ [IFN-γ] in the absence of interleukin-2 [IL-2] or IL-4 secretion). These upregulated cytokines (TNF-a/IFN-γ) largely contributed to upregulation of the apoptosis-inducing cell surface molecule, Fas (APO-1/CD95] and apoptosis induction. The present study investigated the effect of vesnarinone as a novel immunomodulating agent on CD4XL-induced T-cell apoptosis. The addition of vesnarinone to peripheral blood mononuclear cells (PBMC) significantly inhibited CD4XL-induced lymphocyte apoptosis. This apoptosis-inhibitory effect of vesnarinone was associated with the blocking of CD4XL-induced TNF-α and IFN-γ secretion and of Fas antigen upregulation. However, vesnarinone did not block effects of exogenously supplemented TNF-α/IFN-γ on Fas induction. These data suggest that vesnarinone inhibits CD4XL induced TNF-α/IFN-γ secretion, thereby blocking subsequent Fas upregulation and apoptosis induction. Given the potent pathogenic role of imbalanced cytokine secretion observed in HIV-infection, an agent such as vesnarinone may be of therapeutic value in slowing disease progression.

Original languageEnglish (US)
Pages (from-to)2361-2368
Number of pages8
JournalBlood
Volume87
Issue number6
DOIs
StatePublished - Mar 15 1996

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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