Upregulation of expression of the chemokine receptor CCR5 by hydrogen peroxide in human monocytes

• Published in: Mediators of Inflammation 2003-01, Vol.2003 (1), p.29-35
• Main Authors: Lehoux, Geneviève, Le Gouill, Christian, Stankova, Jana, Rola-Pleszczynski, Marek
• Format: Article
• Language: English
• Subjects: c-fos; Catalase - metabolism; Catalase - pharmacology; Cell Membrane - drug effects; Cell Membrane - metabolism; Cells, Cultured; Chemokine CCL4; Chemotaxis; Gene Expression Regulation; Genes, fos - drug effects; Humans; Hydrogen Peroxide - pharmacology; Inflammation - metabolism; Macrophage; Macrophage Inflammatory Proteins - pharmacology; Monocyte; Monocytes - drug effects; Monocytes - physiology; NF-kappa B - antagonists & inhibitors; NF-kappa B - metabolism; Nitriles; Organic Chemicals - pharmacology; Oxidative Stress; Reactive oxygen species; Reactive Oxygen Species - metabolism; Receptors, CCR5 - drug effects; Receptors, CCR5 - genetics; Receptors, CCR5 - metabolism; RNA, Messenger - drug effects; RNA, Messenger - metabolism; Sulfones; Time Factors; Transcriptional Activation; Up-Regulation
• ISSN: 0962-9351; 1466-1861
• DOI: 10.1080/0962935031000096962

The objective of this study was to test the hypothesis that an oxidative stress can serve as a signal to regulate the expression of CCR5. When human monocytes were exposed to graded concentration of hydrogen peroxide (H_2O_2), CCR5 mRNA levels increased maximally at 4 h of exposure to 200 μM of H_2O_2 and decreased by 24 h of treatment. Pretreatment of monocytes with the NF-κB inhibitor BAY 11-8072 blocked the H_2O_2-induced augmentation of CCR5 mRNA expression, suggesting a role for this transcription factor in the regulation of CCR5 expression. CCR5 protein expression on the plasma membrane was also increased by treatment with H_2O_2, as assessed by flow cytometry. This was accompanied by enhanced responsiveness of H_2O_2-pretreated monocytes to the CCR5 ligand MIP-1β in terms of chemotaxis and c-fos gene activation. Our results suggest that oxidative stress may indeed modulate the expression of chemokine receptors and thus contribute to regulation of the inflammatory process.