title: Alpha-Tocopherol counteracts ritonavir-induced proinflammatory cytokines expression in differentiated THP-1 cells.
abstract: 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 alpha-tocopherol (alpha-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 alpha-T supplementation counteracts this effect by suppressing proinflammatory cytokines levels. Here, we report that after differentiating THP-1 cells to macrophages, ritonavir treatment (10 microg/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 muM alpha-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 alpha-T.
authors.affiliation: Vascular Biology Laboratory, JM USDA-HNRCA at Tufts University, Boston, MA 02111, USA. weimin.guo@tufts.edu
authors.forename: Weimin
authors.initials: W
authors.lastname: Guo
authors.forename: Jean Marc
authors.initials: JM
authors.lastname: Zingg
authors.forename: Mohsen
authors.initials: M
authors.lastname: Meydani
authors.forename: Angelo
authors.initials: A
authors.lastname: Azzi
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D002460:Cell Line; D018932:Chemokine CCL2 / Q000235:genetics; D016207:Cytokines / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics; D016209:Interleukin-8 / Q000235:genetics; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019438:Ritonavir / Q000494:pharmacology*; D024502:alpha-Tocopherol / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D016207:Cytokines; D015850:Interleukin-6; D016209:Interleukin-8; D024502:alpha-Tocopherol; D019438:Ritonavir