Methamphetamine modulates DC-SIGN expression by mature dendritic cells.
We report that methamphetamine (meth) may act as cofactor in human immunodeficiency virus (HIV)-1 pathogenesis by increasing dendritic cell (DC)-specific intercellular adhesion molecule-3 (ICAM-3) grabbing non-integrin (DC-SIGN) expression on DCs. Mature DCs (MDCs), obtained from normal subjects, cultured with meth show an up-regulation of DC-SIGN gene and protein expression as analyzed by real-time quantitative polymerase chain reaction and fluorescence-activated cell-sorting analyses, respectively. Furthermore, these meth-induced effects were reversed by a dopamine D1 receptor antagonist (SCH 23390) and small interfering RNA specific to the D1 receptor (D1R) demonstrating that meth-induced effects are mediated through these receptors. Furthermore, meth in synergy with the HIV-1 peptide gp120 up-regulates DC-SIGN gene expression by MDCs. These data are the first evidence that meth up-regulates the expression of DC-SIGN on MDCs. A better understanding of the role of DC-SIGN in HIV-1 infection may help to design novel therapeutic strategies against the progression of HIV-1 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, Kaleida Health System, 100 High Street, Buffalo, NY 14203, USA. mnair@acsu.buffalo.edu
Mahajan
Supriya
S
Sykes
Don
D
Bapardekar
Meghana V
MV
Reynolds
Jessica L
JL
D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003713:Dendritic Cells / Q000187:drug effects*; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D015699:HIV Envelope Protein gp120 / Q000494:pharmacology; D006801:Humans; D037181:Lectins, C-Type / Q000096:biosynthesis / Q000187:drug effects*; D008694:Methamphetamine / Q000494:pharmacology*; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000187:drug effects*; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015815:Cell Adhesion Molecules; D000697:Central Nervous System Stimulants; D015699:HIV Envelope Protein gp120; D037181:Lectins, C-Type; D008694:Methamphetamine; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface; D017447:Receptors, Dopamine D1; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C514793:gp120 protein, Human immunodeficiency virus 1