Journal of Biomedical Science

, Volume 14, Issue 1, pp 59–66

Acyclic nucleoside phosphonate antivirals activate gene expression of monocyte chemotactic protein 1 and 3

Authors

    • Institute of Experimental Medicine, Department of Immunopharmacology, Academy of Sciences of the Czech RepublicCentre for New Antivirals and Antineoplastics
  • Antonín Holý
    • Institute of Organic Chemistry and BiochemistryAcademy of Sciences of the Czech Republic
  • Eva Kmoníčková
    • Institute of Experimental Medicine, Department of Immunopharmacology, Academy of Sciences of the Czech RepublicCentre for New Antivirals and Antineoplastics
    • Institute of Pharmacology, Faculty of MedicineCharles University
  • Jana Křížková
    • Institute of Experimental Medicine, Department of Immunopharmacology, Academy of Sciences of the Czech RepublicCentre for New Antivirals and Antineoplastics
  • Zdeněk Zídek
    • Institute of Experimental Medicine, Department of Immunopharmacology, Academy of Sciences of the Czech RepublicCentre for New Antivirals and Antineoplastics
Article

DOI: 10.1007/s11373-006-9116-4

Cite this article as:
Potměšil, P., Holý, A., Kmoníčková, E. et al. J Biomed Sci (2007) 14: 59. doi:10.1007/s11373-006-9116-4

Summary

Acyclic nucleoside phosphonates are potent antiviral agents effective against replication of DNA viruses and retroviruses including human immunodeficiency virus (HIV). In addition to their antimetabolic mode of antiviral action, acyclic nucleoside phosphonates also possess immunomodulatory properties. We have shown recently that a number of them stimulate secretion of cytokines including chemokines RANTES/CCL5 (“regulated upon activation, normal T cell expressed and secreted”) and MIP-1 alpha/CCL3 (macrophage inflammatory protein-1 alpha) that may inhibit entry of HIV in cells. In present experiments we analyzed effects of acyclic nucleoside phosphonates on gene expression of other members of the beta family of chemokines, monocyte chemotactic proteins (MCPs), which have also been implicated in the control of HIV infection. The following compounds differing at the type of heterocyclic base, i.e. adenine (A), or 2,6-diaminopurine (DAP), at the 6-amino group of the base, and at the N9-side chain represented by 9-[2-(phosphonomethoxy)ethyl] (PME) and 9-[2-(phosphonomethoxy)propyl] (PMP) moieties were included in the study: (1) (R)-PMPA, ie. tenofovir, (2) N6-cyclopropyl-(R)-PMPDAP, (3) N6-cyclopentyl-(R)-PMPDAP, (4) N6-dimethylaminoethyl-(R)-PMPDAP, (5) N6-cyclopentyl-PMEDAP, (6) N6-isobutyl-PMEDAP, (7) N6-cyclohexylmetyl-PMEDAP, and (8) N6-cyclooctyl-PMEDAP. These compounds are able to activate production of MCP-1 and MCP-3, and none of them influences gene expression of MCP-2, and MCP-5. Enhancement of monocyte chemotactic protein expression was found to be mediated by transcriptional factor nuclear factor-κB (NF-κB).

Key words

acyclic nucleoside phosphonateHIVmonocyte chemotactic proteinnuclear factor-κB

Copyright information

© National Science Council Taipei 2006