Methamphetamine Inhibits β-Chemokines and Co-Stimulatory Molecule Expression by Dendritic Cells
- 1 Florida International University, United States
- 2 Universida Central del Caribe School of Medicine, United States
- 3 State University of New York at Buffalo, United States
- 4 Mount Sinai Medical Center, United States
Abstract
The US is currently experiencing a serious epidemic of methamphetamine (Meth) use entangled with HIV-1 infection. Blood monocyte derived dendritic cells (DC ) are the first line of defense against HIV-1 infection and are the initial target of HIV-1 in injection drug users. Chemokines are known to be HIV-1 suppressing molecules and are positively associated with non- progression of HIV disease. Co-stimulatory molecules are necessary for DC maturation, effective antigen presentation, cell migration, and T cell proliferation. Although previous studies suggest that Meth deregulates various immune responses, the role of Meth on gene expression and production of β-chemokines and co-stimulatory molecules by DC has not been studied. We hypothesize that Meth induced immune defects may be mediated by dysregulation of β-chemokines (MIP-1α/CCL3, MIP-1β/CCL4 and RANTES/CCL5), co-stimulatory and maturation molecules (CD83 and CCR7) by DC. Our results show that Meth significantly downregulates the gene expression and production of β-chemokines and co stimulatory molecule by DC from normal subjects. In HIV-1 infected subjects, RANTES variant In1.1c that has been associated with accelerated HIV-1 disease progression was significantly higher compared to normal controls. Further, Meth significantly inhibited total RANTES gene expression with a reciprocal upregulation of RANTES variant In1.1c in a dose dependent manner by both immature DC (IDC) and mature DC (MDC) from normal subjects. These studies report for the first time that Meth deregulates β-chemokines and co-stimulatory molecule expression by DC. The results emanating from these studies may help to support the therapeutic application of chemokines to restore anti-HIV-1 immune responses to prevent or control HIV-1 infection in meth using populations.
DOI: https://doi.org/10.3844/ajidsp.2007.217.224
Copyright: © 2007 Madhavan P.N. Nair, Jose W. Rodriguez, Irina M. Borodowsky, Supriya Mahajan, Narayanan Nair, Tolu T. Dada, Alain Diaz-Gonzalez and Paul Katz. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Keywords
- DC-SIGN
- dendritic cell(DC) specific C type ICAM-3 grabbing nonintegrin
- RANTES
- regulated upon activation T-cell expressed and secreted
- IDC immature DC
- MDC
- mature DC