Host chemokine (C-C motif) ligand-2 (CCL2) is differentially regulated in HIV type 1 (HIV-1)-infected individuals.

Abstract:

:Several cytokines and chemokines including chemokine (C-C motif) ligand-2 (CCL2) are induced in HIV-1 infection. However, the impact of HIV-1 viremia on CCL2 regulation is largely unknown. We utilized a DNA oligonucleotide microarray covering 110 inflammatory genes. Five genes were induced by at least 2-fold in PBMCs of HIV-1 viremic (>100,000 RNA copies ml(-1)) as compared with aviremic (<50 RNA copies ml(-1)) individuals. These genes were CCL2, CXC chemokine ligand-10, IFN-gamma, GTP-cyclohydrolase-1 and C-C chemokine receptor-1. In addition to microarray data verification by real-time PCR, analysis of independent patient samples revealed a similar expression pattern. CCL2 was the most strongly regulated gene at mRNA level and its serum concentration was significantly elevated in viremic compared with aviremic and HIV-1 seronegative controls, indicating a positive correlation between viremia and CCL2. Flow cytometric studies demonstrated a higher percentage of CCL2-expressing CD14(+) monocytes in viremic compared with aviremic individuals. These results suggest a highly restricted modulation of host inflammatory gene response by HIV. Genes up-regulated in the viremic state, in particular CCL2, presumably serve as potential enhancing factors in HIV-1 replication, represented by high viral load in HIV-1 viremic patients. Inhibition of increased CCL2 production could provide a new therapeutic intervention in HIV-1 infection.

journal_name

Int Immunol

journal_title

International immunology

authors

Ansari AW,Bhatnagar N,Dittrich-Breiholz O,Kracht M,Schmidt RE,Heiken H

doi

10.1093/intimm/dxl078

subject

Has Abstract

pub_date

2006-10-01 00:00:00

pages

1443-51

issue

10

eissn

0953-8178

issn

1460-2377

pii

dxl078

journal_volume

18

pub_type

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