Premium
Inhibition of HIV protease inhibitor‐induced inflammatory response and ER stress by raltegravir in macrophages
Author(s) -
Zhao Renping,
Zhang Xiaoxuan,
Cao Risheng,
Hylemon Phillip B,
Pandak William M,
Zhang Luyong,
Wang Guangji,
Zhou Huiping
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.995.1
Subject(s) - raltegravir , integrase inhibitor , ritonavir , pharmacology , protease inhibitor (pharmacology) , western blot , unfolded protein response , dyslipidemia , chemistry , biology , virology , viral load , human immunodeficiency virus (hiv) , biochemistry , endocrinology , endoplasmic reticulum , antiretroviral therapy , gene , obesity
Our previous studies suggest that the HIV protease inhibitor (PI)‐induced ER stress and inflammatory response in macrophages represents an important cellular mechanism of highly active anti‐retroviral therapy (HAART)‐induced dyslipidemia and atherosclerosis. Raltegravir is the first member of the newest class of anti‐HIV drugs, HIV integrase inhibitor. Our recent studies indicate that raltegravir has less hepatic toxicity and could prevent HIV PI‐induced dysregulation of lipid metabolism by inhibiting ER stress in hepatocytes. However, whether raltegravir is also able to prevent HIV PI‐induced inflammatory response, ER stress and lipid accumulation in macrophages remains unclear and is the focus of this study. Methods J774A.1 mouse macrophages and human THP‐1‐derived macrophages were treated with HIV PIs (lopinavir/ritonavir) with or without raltegravir. The mRNA and protein levels of TNF‐α and IL‐6 were measured by real‐time RT‐PCR and ELISA, respectively. Activation of ER stress was detected by real‐time RT‐PCR and Western blot analysis. Intracellular lipid was detected using oil‐red O staining. Results Raltegravir not only significantly inhibited HIV PI‐induced TNF‐α and IL‐6 expression and ER stress activation, but also reduced HIV PI‐induced foaming cell formation. Conclusions Incorporation of raltegravir in HAART may reduce HIV PI‐PI‐induced dyslipidemia and atherosclerosis.