berberine inhibits hiv protease inhibitor-induced inflammatory response by modulating er stress signaling pathways in murine macrophages小檗碱抑制hiv蛋白酶inhibitor-induced炎症反应的调节er应激小鼠巨噬细胞的信号通路.pdfVIP

Berberine Inhibits HIV Protease Inhibitor-Induced Inflammatory Response by Modulating ER Stress Signaling Pathways in Murine Macrophages 1,2 1,3 1,3 1 1 1 Weibin Zha , Guang Liang , Jian Xiao , Elaine J. Studer , Phillip B. Hylemon , William M. Pandak, Jr. , 3 3 1,3 Guangji Wang *, Xiaokun Li , Huiping Zhou * 1 Department of Microbiology Immunology and Internal Medicine/Gastroenterology and McGuire Veterans Affairs Medical Center, Virginia Commonwealth University, Richmond, Virginia, United States of America, 2 China Pharmaceutical University, Nanjing, China, 3 School of Pharmacy, Wenzhou Medical College, Wenzhou, China Abstract Background: HIV protease inhibitor (PI)-induced inflammatory response plays an important role in HIV PI-associated dyslipidemia and cardiovascular complications. This study examined the effect of berberine, a traditional herb medicine, on HIV PI-induced inflammatory response and further investigated the underlying cellular/molecular mechanisms in macrophages. Methodology and Principal Findings: Cultured mouse J774A.1 macrophages and primary mouse macrophages were used in this study. The expression of TNF-a and IL-6 were detected by real-time RT-PCR and ELISA. Activations of ER stress and ERK signaling pathways were determined by Western blot analysis. Immunofluorescent staining was used to determine the intracellular localization of RNA binding protein HuR. RNA-pull down assay was used to determine the association of HuR with endogenous TNF-a and IL-6. Berberine significantly inhibited HIV PI-induced TNF-a and IL-6 expression by modulating