- 作者: Petr Potmesil; Anton璯 Holy; Eva Kmon獳kov? Jana Krizkova; Zdenek Zidek
- 作者服務機構: l Institute of Experimental Medicine, Department of Immunopharmacology, Academy of Sciences of the Czech Republic, Centre for New Antivirals and Antineoplastics, V獮e雟k?1083, 142 20, Prague 4 Czech Republic; ; 2 Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nam. 2, 166 10, Prague 6 Czech Republic; ; 3 Institute of Pharmacology, Faculty of Medicine, Charles University, Karlovarska 48, 301 66, Pilsen Czech Republic
- 中文摘要: --
- 英文摘要: 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-CyclopentyHiv)-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-κΒ (NF-κΒ).
- 中文關鍵字: --
- 英文關鍵字: acyclic nucleoside phosphonate, HIV, monocyte chemotactic protein, nuclear factor-κΒ