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S-nitrosoglutathione modulates CXCR4 and ICOS expression

Abstract

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.

Abbreviations

SNG:

S-nitrosoglutathione

PMA:

phorbol 12-myristate 13-acetate

V-ATPase:

vacuolar H+-ATPase

ICOS:

inducible co-stimulator

HIV:

human immunodeficiency virus

CCP:

clathlin-coated pit

PBMC:

peripheral mononuclear cells

GRK:

G-protein coupled receptor kinase

References

  1. 1.

    Anderson, R.G. and Orci, L. A view of acidic intracellular compartments. J. Cell Biol. 106 (1988) 539–543.

  2. 2.

    Feng, Y. and Forgac, M. A novel mechanism for regulation of vacuolar acidification. J. Biol. Chem. 267 (1992) 19769–19772.

  3. 3.

    Forgac, M. The vacuolar H+-ATPase of clathrin-coated vesicles is reversibly inhibited by S-nitrosoglutathione. J. Biol. Chem. 274 (1999) 1301–1305.

  4. 4.

    Feng, Y., Broder, C.C., Kennedy, P.E. and Berger, E.A. HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science 272 (1996) 872–877.

  5. 5.

    Orsini, M.J., Parent, J.L., Mundell, S.J., Benovic, J.L. and Marchese, A. Trafficking of the HIV coreceptor CXCR4. Role of arrestins and identification of residues in the c-terminal tail that mediate receptor internalization. J. Biol. Chem. 274 (1999) 31076–31086.

  6. 6.

    Hutloff, A., Dittrich, A.M., Beier, K.C., Eljaschewitsch, B., Kraft, R., Anagnostopoulos, I. and Kroczek, R.A. ICOS is an inducible T-cell co-stimulator structurally and functionally related to CD28. Nature 397 (1999) 263–236.

  7. 7.

    Swigut, T., Shohdy, N. and Skowronski, J. Mechanism for down-regulation of CD28 by Nef. EMBO J. 20 (2001) 1593–1604.

  8. 8.

    Mueller, A., Kelly, E. and Strange, P.G. Pathways for internalization and recycling of the chemokine receptor CCR5. Blood 99 (2002) 785–791

  9. 9.

    Lu, X., Yu, H., Liu, S.H., Brodsky, F.M. and Peterlin, B.M. Interactions between HIV1 Nef and vacuolar ATPase facilitate the internalization of CD4. Immunity 8 (1998) 647–656.

  10. 10.

    Aiken, C., Konner, J., Landau, N.R., Lenburg, M.E. and Trono, D. Nef induces CD4 endocytosis: requirement for a critical dileucine motif in the membrane-proximal CD4 cytoplasmic domain. Cell 76 (1994) 853–864.

  11. 11.

    Geyer, M., Yu, H., Mandic, R., Linnemann, T., Zheng, Y. H., Fackler, O.T. and Peterlin B.M. Subunit H of the V-ATPase binds to the medium chain of adaptor protein complex 2 and connects Nef to the endocytic machinery. J. Biol. Chem. 277 (2002) 28521–28529.

  12. 12.

    Luo, T., Fredericksen, B.L., Hasumi, K., Endo, A. and Garcia, J.V. Human immunodeficiency virus type 1 Nef-induced CD4 cell surface downregulation is inhibited by ikarugamycin. J. Virol. 75 (2001) 2488–2492.

  13. 13.

    Hasumi, K., Shinohara, C., Naganuma, S. and Endo, A. Inhibition of the uptake of oxidized low-density lipoprotein in macrophage J774 by the antibiotic ikarugamycin. Eur. J. Biochem. 205 (1992) 841–846.

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Key words

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