α-Tocopherol counteracts ritonavir-induced proinflammatory cytokines expression in differentiated THP-1 cells
Article first published online: 19 DEC 2008
Copyright © 2007 International Union of Biochemistry and Molecular Biology, Inc.
Volume 31, Issue 3-4, pages 171–179, 2007
How to Cite
Guo, W., Zingg, J. M., Meydani, M. and Azzi, A. (2007), α-Tocopherol counteracts ritonavir-induced proinflammatory cytokines expression in differentiated THP-1 cells. BioFactors, 31: 171–179. doi: 10.1002/biof.5520310304
- Issue published online: 19 DEC 2008
- Article first published online: 19 DEC 2008
- Manuscript Accepted: 11 JUN 2008
- Manuscript Revised: 10 JUN 2008
- Manuscript Received: 3 MAY 2008
- US Department of Agriculture. Grant Number: 58–1950–7–707
- inflammatory cytokines;
- THP-1 cells
Treatment of HIV-infected individuals with HIV protease inhibitor (HPI) drugs has significantly increased their life span. However, one of the side effects of HPI drugs is the development of premature atherosclerosis, whose molecular pathogenesis remains unclear. Previously we have reported that α-tocopherol (α-T) normalizes CD36 overexpression induced by ritonavir treatment and reduces oxLDL uptake in THP-1 cells. Since inflammation is a major player in the pathogenesis of atherosclerosis, we hypothesized that HPI drugs, such as ritonavir, increase proinflammatory cytokines synthesis and that α-T supplementation counteracts this effect by suppressing proinflammatory cytokines levels. Here, we report that after differentiating THP-1 cells to macrophages, ritonavir treatment (10 μg/mL) significantly increases expression of proinflammatory cytokines, IL-6, MCP-1 and IL-8, at both mRNA and protein levels. This ritonavir-induced effect is significantly suppressed by treatment of THP-1/macrophages with 50 μM α-T. We conclude that ritonavir can induce proinflammatory cytokines synthesis in THP-1/macrophages, which might be associated with the development of premature atherosclerosis in ritonavir-treated patients and that this effect is prevented by α-T.