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.

• Authors: 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
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 174 Issue 11 Pg. 6617-26 (Jun 01 2005) ISSN: 0022-1767 [Print] United States
• PMID: 15905500 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antigens, CD
• CLEC4M protein, human
• Cell Adhesion Molecules
• DC-specific ICAM-3 grabbing nonintegrin
• Dopamine Antagonists
• Gene Products, tat
• HIV Envelope Protein gp120
• ICAM3 protein, human
• Lectins, C-Type
• Receptors, Cell Surface
• Receptors, Dopamine
• tat Gene Products, Human Immunodeficiency Virus
• Mitogen-Activated Protein Kinases
• Cocaine

Topics

• Antigens, CD (metabolism)
• Cell Adhesion Molecules (biosynthesis, genetics)
• Cell Differentiation (drug effects, immunology)
• Cocaine (pharmacology)
• Dendritic Cells (drug effects, immunology, metabolism, virology)
• Dopamine Antagonists (pharmacology)
• Drug Synergism
• Gene Expression Regulation (drug effects, immunology)
• Gene Products, tat (pharmacology)
• HIV Envelope Protein gp120 (pharmacology)
• HIV Infections (enzymology, immunology, metabolism, pathology)
• HIV-1 (drug effects, immunology)
• Humans
• Lectins, C-Type (biosynthesis, genetics)
• MAP Kinase Signaling System (drug effects, immunology)
• Mitogen-Activated Protein Kinases (antagonists & inhibitors, physiology)
• Receptors, Cell Surface (biosynthesis, genetics)
• Receptors, Dopamine (metabolism)
• Virus Replication (drug effects, immunology)
• tat Gene Products, Human Immunodeficiency Virus