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α‐Tocopherol counteracts ritonavir‐induced proinflammatory cytokines expression in differentiated THP‐1 cells
Author(s) -
Guo Weimin,
Zingg Jean Marc,
Meydani Mohsen,
Azzi Angelo
Publication year - 2007
Publication title -
biofactors
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.204
H-Index - 94
eISSN - 1872-8081
pISSN - 0951-6433
DOI - 10.1002/biof.5520310304
Subject(s) - proinflammatory cytokine , ritonavir , thp1 cell line , inflammation , tumor necrosis factor alpha , pathogenesis , immunology , pharmacology , medicine , biology , cell culture , human immunodeficiency virus (hiv) , viral load , antiretroviral therapy , genetics
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.