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Cocaine modulates dendritic cell-specific C type intercellular adhesion molecule-3-grabbing nonintegrin expression by dendritic cells in HIV-1 patients.

Abstract

We report that cocaine may act as cofactor in HIV pathogenesis by increasing dendritic cell-specific C type ICAM-3-grabbing nonintegrin (DC-SIGN) expression on dendritic cells (DC). Our results show that cocaine-using, long-term nonprogressors and normal progressors of HIV infection manifest significantly higher levels of DC-SIGN compared with cocaine-nonusing long-term nonprogressors and normal progressors, respectively. Furthermore, in vitro HIV infection of MDC from normal subjects cultured with cocaine and/or HIV peptides up-regulated DC-SIGN, confirming our in vivo finding. Cocaine, in synergy with HIV peptides, also up-regulates DC-SIGN gene expression by MDC. Furthermore, the cocaine-induced effects were reversed by a D1 receptor antagonist demonstrating the specificity of the reaction. Our results indicate that cocaine exacerbates HIV infection by up-regulating DC-SIGN on DC and these effects are mediated via dysregulation of MAPKs. These data are the first evidence that cocaine up-regulates the expression of DC-SIGN on DC. A better understanding of the role of DC-SIGN in HIV infection may help to design novel therapeutic strategies against the progression of HIV disease in the drug-using population.

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BibTeXRIS

Madhavan P N Nair, Supriya D Mahajan, Stanley A Schwartz, Jessica Reynolds, Robert Whitney, Zail Bernstein, Ram P Chawda, Don Sykes, Ross Hewitt, Chiu Bin Hsiao. 2005-06-01. Cocaine modulates dendritic cell-specific C type intercellular adhesion molecule-3-grabbing nonintegrin expression by dendritic cells in HIV-1 patients.. https://doi.org/10.4049/jimmunol.174.11.6617

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