Effect of methamphetamine on expression of HIV coreceptors and CC-chemokines by dendritic cells

The United States is currently experiencing an entangled epidemic of HIV infection and use of different drugs of abuse, especially of methamphetamine (Meth). Blood monocyte-derived dendritic cells (DC) are the first line of defense against HIV-1 infection, and are the initial target of HIV-1 infecti...

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Veröffentlicht in:Life sciences (1973) 2011-05, Vol.88 (21), p.987-994
Hauptverfasser: Nair, Madhavan P.N., Saiyed, Zainulabedin M.
Format: Artikel
Sprache:eng
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Zusammenfassung:The United States is currently experiencing an entangled epidemic of HIV infection and use of different drugs of abuse, especially of methamphetamine (Meth). Blood monocyte-derived dendritic cells (DC) are the first line of defense against HIV-1 infection, and are the initial target of HIV-1 infection in injection drug users. DC-SIGN present on dendritic cells is the first molecule that facilitates HIV-1 infection independent of CD4 or HIV coreceptors. Aims: The aim of this study was to evaluate whether Meth acts as a cofactor in the pathogenesis of HIV-1 infection. Main methods: Monocyte derived DCs, obtained from normal subjects were cultured with and without Meth ± HIV-1B, followed by analyzing the gene and protein expression by real-time quantitative polymerase chain reaction (RT-PCR) and fluorescence-activated cell-sorting analyses, respectively. Key findings: Our results show that Meth significantly enhances HIV infection, and downregulates the gene expression of chemokines and costimulatory molecules with reciprocal upregulation of HIV coreceptors and DC-SIGN by dendritic cells. Significance: Better understanding of the role of Meth in HIV-1 disease susceptibility and the mechanism through which Meth mediates its effects on HIV-1 infection may help to devise novel therapeutic strategies against HIV-1 infection in Meth using HIV-1 infected population.
ISSN:0024-3205
1879-0631
DOI:10.1016/j.lfs.2010.09.019