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| Titel: |
Methamphetamine Inhibits Beta-Chemokines and Co-Stimulatory Molecule Expression by Dendritic Cells |
| Auteur: |
Madhavan P.N Nair Jose W. Rodriguez Irina M. Borodowsky Supriya Mahajan Narayanan Nair Tolu T. Dada Alain Diaz-Gonzalez Paul Katz |
| Verschenen in: |
American journal of infectious diseases |
| Paginering: | Jaargang 3 (2007) nr. 4 pagina's 217-224 |
| Jaar: |
2007 |
| Inhoud: |
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 ofdefense 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 ofHIV disease. Co-stimulatory molecules are necessary for DC maturation, effective antigen presentation, cell migration, and T cell proliferation. Although previous studies suggest that Methderegulates various immune responses, the role of Meth on gene expression and production of - chemokines and co-stimulatory molecules by DC has not been studied. We hypothesize that Methinduced immune defects may be mediated by dysregulation of -chemokines (MIP-1/CCL3, MIP- 1b/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 - 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 RANTESgene 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 thefirst time that Meth deregulates -chemokines and co-stimulatory molecule expression by DC. The results emanating from these studies may help to support the therapeutic application of chemokines torestore anti-HIV-1 immune responses to prevent or control HIV-1 infection in meth using populations. |
| Uitgever: |
Science Publications (provided by DOAJ) |
| Bronbestand: |
Elektronische Wetenschappelijke Tijdschriften |
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