Affiliations: Vascular Biology Laboratory, JM USDA-HNRCA at Tufts
University, Boston, MA, USA
Note: [] Address for correspondence: Dr. Weimin Guo, Vascular Biology
Laboratory, Office 621, JM USDA-HNRCA at Tufts University, 711 Washington
Street, Boston, MA 02111, USA. Tel.: +1 617 556 3229; Fax: +1 617 556 3224;
E-mail: weimin.guo@tufts.edu
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
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.
