title: Methamphetamine and HIV-1 gp120 effects on lipopolysaccharide stimulated matrix metalloproteinase-9 production by human monocyte-derived macrophages.
abstract: Monocytes/macrophages are a primary source of human immunodeficiency virus (HIV-1) in the central nervous system (CNS). Macrophages infected with HIV-1 produce a plethora of factors, including matrix metalloproteinase-9 (MMP-9) that may contribute to the development of HIV-1-associated neurocognitive disorders (HAND). MMP-9 plays a pivotal role in the turnover of the extracellular matrix (ECM) and functions to remodel cellular architecture. We have investigated the role of methamphetamine and HIV-1 gp120 in the regulation of lipopolysaccaride (LPS) induced-MMP-9 production in monocyte-derived macrophages (MDM). Here, we show that LPS-induced MMP-9 gene expression and protein secretion are potentiated by incubation with methamphetamine alone and gp120 alone. Further, concomitant incubation with gp120 and methamphetamine potentiated LPS-induced MMP-9 expression and biological activity in MDM. Collectively methamphetamine and gp120 effects on MMPs may modulate remodeling of the extracellular environment enhancing migration of monocytes/macrophages to the CNS.
authors.affiliation: Departments of Medicine, Division of Allergy, Immunology and Rheumatology, State University of New York at Buffalo, Innovation Center, USA. jlr8@buffalo.edu
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Reynolds
authors.forename: Supriya D
authors.initials: SD
authors.lastname: Mahajan
authors.forename: Ravikumar
authors.initials: R
authors.lastname: Aalinkeel
authors.forename: Bindukumar
authors.initials: B
authors.lastname: Nair
authors.forename: Donald E
authors.initials: DE
authors.lastname: Sykes
authors.forename: Stanley A
authors.initials: SA
authors.lastname: Schwartz
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects*; D015699:HIV Envelope Protein gp120 / Q000494:pharmacology*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D008694:Methamphetamine / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D000697:Central Nervous System Stimulants; D015699:HIV Envelope Protein gp120; D008070:Lipopolysaccharides; D008694:Methamphetamine; D048051:p38 Mitogen-Activated Protein Kinases; D020780:Matrix Metalloproteinase 9