Cocaine modulates dendritic cell-specific C type intercellular adhesion molecule-3-grabbing nonintegrin expression by dendritic cells in HIV-1 patients.
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.
Nair
Madhavan P N
MP
Department of Medicine, Division of Allergy, Immunology, and Rheumatology, State University of New York and Buffalo General Hospital, 14203, USA. mnair@acsu.buffalo.edu
Mahajan
Supriya D
SD
Schwartz
Stanley A
SA
Reynolds
Jessica
J
Whitney
Robert
R
Bernstein
Zail
Z
Chawda
Ram P
RP
Sykes
Don
D
Hewitt
Ross
R
Hsiao
Chiu Bin
CB
D015703:Antigens, CD / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D003042:Cocaine / Q000494:pharmacology*; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004357:Drug Synergism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D015696:Gene Products, tat / Q000494:pharmacology; D015699:HIV Envelope Protein gp120 / Q000494:pharmacology; D015658:HIV Infections / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D037181:Lectins, C-Type / Q000096:biosynthesis* / Q000235:genetics; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000276:immunology; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000235:genetics; D011954:Receptors, Dopamine / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects / Q000276:immunology; D054322:tat Gene Products, Human Immunodeficiency Virus; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D003042:Cocaine; D018492:Dopamine Antagonists; D015696:Gene Products, tat; D015699:HIV Envelope Protein gp120; D037181:Lectins, C-Type; D020928:Mitogen-Activated Protein Kinases; D011956:Receptors, Cell Surface; D011954:Receptors, Dopamine; D054322:tat Gene Products, Human Immunodeficiency Virus; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C433029:CLEC4M protein, human; C483616:ICAM3 protein, human