Research Article Open Access

Methamphetamine Inhibits β-Chemokines and Co-Stimulatory Molecule Expression by Dendritic Cells

Madhavan P.N. Nair1, Jose W. Rodriguez1, Irina M. Borodowsky2, Supriya Mahajan3, Narayanan Nair1, Tolu T. Dada1, Alain Diaz-Gonzalez1 and Paul Katz4
  • 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.

American Journal of Infectious Diseases
Volume 3 No. 4, 2007, 217-224

DOI: https://doi.org/10.3844/ajidsp.2007.217.224

Submitted On: 24 June 2007 Published On: 31 December 2007

How to Cite: Nair, M. P., Rodriguez, J. W., Borodowsky, I. M., Mahajan, S., Nair, N., Dada, T. T., Diaz-Gonzalez, A. & Katz, P. (2007). Methamphetamine Inhibits β-Chemokines and Co-Stimulatory Molecule Expression by Dendritic Cells. American Journal of Infectious Diseases, 3(4), 217-224. https://doi.org/10.3844/ajidsp.2007.217.224

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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