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.
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
Madhavan P N
MP
Nair
Supriya
S
Mahajan
Don
D
Sykes
Meghana V
MV
Bapardekar
Jessica L
JL
Reynolds
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