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Methamphetamine Modulates Gene Expression Patterns in Monocyte Derived Mature Dendritic Cells

Implications for HIV-1 Pathogenesis

Molecular Diagnosis & Therapy volume 10, pages 257–269 (2006)Cite this article

Abstract

Background: The US is currently experiencing a grave epidemic of methamphetamine use as a recreational drug, and the risk for HIV-1 infection attributable to methamphetamine use continues to increase. Recent studies show a high prevalence of HIV infection among methamphetamine users. Dendritic cells (DCs) are potent antigen presenting cells that are the initial line of defense against HIV-1 infection. In addition, DCs also serve as reservoirs for HIV-1 and function at the interface between the adaptive and the innate immune systems, which recognize and internalize pathogens and subsequently activate T cells. Exposure to methamphetamine results in modulation of immune functional parameters that are necessary for host defense. Chronic methamphetamine use can cause psychiatric co-morbidity, neurological complications, and can alter normal biological processes and immune functions. Limited information is available on the mechanisms by which methamphetamine may influence immune function. This study explores the effect of methamphetamine on a specific array of genes that may modulate immune function. We hypothesize that methamphetamine treatment results in the immunomodulation of DC functions, leading to dysregulation of the immune system of the infected host. This suggests that methamphetamine has a role as a cofactor in the pathogenesis of HIV-1.

Methods: We used the high-throughput technology of gene microarray analysis to understand the molecular mechanisms underlying the genomic changes that alter normal biological processes when DCs are treated with methamphetamine. Additionally, we validated the results obtained from microarray experiments using a combination of quantitative real-time PCR and Western blot analysis.

Results: These data are the first evidence that methamphetamine modulates DC expression of several genes. Methamphetamine treatment alters categories of genes that are associated with chemokine regulation, cytokinesis, signal transduction mechanisms, apoptosis, and cell cycle regulation. This report focuses on a selected group of genes that are significantly modulated by methamphetamine treatment and that have been associated with HIV-1 pathogenesis.

Discussion/Conclusion: The purpose of this study was to identify genes that are unique and/or specific to the complex immunomodulatory mechanisms that are altered as a result of methamphetamine abuse in HIV-1-infected patients. These studies will help to identify the molecular mechanisms that underlie methamphetamine toxicity, and several functionally important classes of genes have emerged as targets in methamphetamine-mediated immunopathogenesis of HIV-1. Identification of novel DC-specific and methamphetamine-responsive genes that modulate several biological, molecular, and signal transduction functions may serve as methamphetamine- and/or HIV-1-specific drug targets.

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Acknowledgements

This work was supported by NIDA grants RO1 DA-12366, 14218, 15628, and the Kaleida Health Cameron Troup Fund Grant #71016.

The authors have no conflicts of interest that are directly relevant to the content of this article.

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Affiliations

  1. Department of Medicine, Division of Allergy, Immunology, and Rheumatology, Buffalo General Hospital, 310 Multi Research Building, 100 High Street, Buffalo, New York, 14203, USA

    Supriya D. Mahajan, Jessica L. Reynolds, Ravikumar Aalinkeel, Stanley A. Schwartz & Madhavan P. N. Nair

  2. Department of Biostatistics, Department of Medicine, Center for Computational Research, University at Buffalo, State University of New York (SUNY), Buffalo, New York, USA

    Zihua Hu

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  1. Supriya D. Mahajan
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  2. Zihua Hu
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Correspondence to Supriya D. Mahajan.

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Mahajan, S.D., Hu, Z., Reynolds, J.L. et al. Methamphetamine Modulates Gene Expression Patterns in Monocyte Derived Mature Dendritic Cells. Mol Diag Ther 10, 257–269 (2006). https://doi.org/10.1007/BF03256465

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Keywords

  • Methamphetamine
  • Mature Dendritic Cell
  • Signal Transduction Molecule
  • Methamphetamine User
  • Potent Antigen Present Cell