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S-nitrosoglutathione modulates CXCR4 and ICOS expression


The expression of CXCR4, a membrane protein which is involved in the entry of HIV-1, is down-modulated from the cell surface by Phorbol 12-myristate 13-acetate (PMA) and the Ca+ ionophore, Ionomycin. Inducible co-stimulator (ICOS), which contributes to lymphocyte proliferation, is up-regulated by PMA/Ionomycin. We examined the influence of S-nitrosoglutathione (SNG), an inhibitor of Vacuolar H+-ATPase (V-ATPase), on the expression of CXCR4 and ICOS in PMA/Ionomycin-treated peripheral mononuclear cells (PBMC), and of CXCR4 alone in lymphoid cell lines. In this report, we show that SNG interferes with both effects of PMA/Ionomycin, namely CXCR4 down-regulation and ICOS up-regulation. These studies imply opposing roles of V-ATPase in the regulation of CXCR4 and ICOS. The influence of SNG in modulating the susceptibility of T cells to HIV-1 and on their immune responses needs further investigation.





phorbol 12-myristate 13-acetate


vacuolar H+-ATPase


inducible co-stimulator


human immunodeficiency virus


clathlin-coated pit


peripheral mononuclear cells


G-protein coupled receptor kinase


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Yamamoto, Y., Pahwa, R. & Pahwa, S. S-nitrosoglutathione modulates CXCR4 and ICOS expression. Cell. Mol. Biol. Lett. 11, 30–36 (2006).

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Key words

  • S-nitrosoglutathione (SNG)
  • CXCR4
  • ICOS
  • HIV-1