PMID- 16884330
OWN - NLM
STAT- MEDLINE
DCOM- 20061016
LR  - 20181113
IS  - 1177-1062 (Print)
IS  - 1177-1062 (Linking)
VI  - 10
IP  - 4
DP  - 2006
TI  - Methamphetamine modulates gene expression patterns in monocyte derived mature 
      dendritic cells: implications for HIV-1 pathogenesis.
PG  - 257-69
AB  - 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.
FAU - Mahajan, Supriya D
AU  - Mahajan SD
AD  - Department of Medicine, Division of Allergy, Immunology, and Rheumatology, 
      Buffalo General Hospital, Buffalo, New York 14203, USA. smahajan@buffalo.edu
FAU - Hu, Zihua
AU  - Hu Z
FAU - Reynolds, Jessica L
AU  - Reynolds JL
FAU - Aalinkeel, Ravikumar
AU  - Aalinkeel R
FAU - Schwartz, Stanley A
AU  - Schwartz SA
FAU - Nair, Madhavan P N
AU  - Nair MP
LA  - eng
GR  - 14218/PHS HHS/United States
GR  - 15628/PHS HHS/United States
GR  - R01 DA-12366/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - New Zealand
TA  - Mol Diagn Ther
JT  - Molecular diagnosis & therapy
JID - 101264260
RN  - 0 (Central Nervous System Stimulants)
RN  - 0 (Chemokines)
RN  - 0 (Cytokines)
RN  - 0 (Receptors, Chemokine)
RN  - 44RAL3456C (Methamphetamine)
SB  - IM
MH  - Adult
MH  - Amphetamine-Related Disorders/genetics/*immunology
MH  - Central Nervous System Stimulants/*pharmacology
MH  - Chemokines/genetics
MH  - Cytokines/genetics
MH  - Dendritic Cells/drug effects/immunology
MH  - Gene Expression/*drug effects
MH  - Gene Expression Profiling
MH  - HIV Infections/genetics/*immunology
MH  - *HIV-1
MH  - Humans
MH  - Immunity/*genetics
MH  - Methamphetamine/*pharmacology
MH  - Monocytes/drug effects/immunology
MH  - Oligonucleotide Array Sequence Analysis
MH  - Receptors, Chemokine/genetics
EDAT- 2006/08/04 09:00
MHDA- 2006/10/17 09:00
CRDT- 2006/08/04 09:00
PHST- 2006/08/04 09:00 [pubmed]
PHST- 2006/10/17 09:00 [medline]
PHST- 2006/08/04 09:00 [entrez]
AID - 1047 [pii]
AID - 10.1007/BF03256465 [doi]
PST - ppublish
SO  - Mol Diagn Ther. 2006;10(4):257-69. doi: 10.1007/BF03256465.