Journal
IMMUNOLOGICAL INVESTIGATIONS
Volume 40, Issue 5, Pages 481-497Publisher
TAYLOR & FRANCIS INC
DOI: 10.3109/08820139.2011.559499
Keywords
Methamphetamine; Monocyte-derived mature macrophages; Lipopolysaccharide; Matrix metalloproteinase; gp120; Human immunodeficiency virus
Categories
Funding
- Kaleida Health Foundation
- [K01 DA024577]
- [R01AI085569]
- [R21DA030108]
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI085569] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON DRUG ABUSE [K01DA024577, R21DA030108] Funding Source: NIH RePORTER
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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.
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