Berberine Inhibits HIV Protease Inhibitor-Induced Inflammatory Response by Modulating ER Stress Signaling Pathways in Murine Macrophages

Authors

Weibin Zha, Virginia Commonwealth University, China Pharmaceutical University
Guang Liang, Virginia Commonwealth University, Wenzhou Medical College
Jian Xiao, Virginia Commonwealth University,Wenzhou Medical College
Elaine Studer, Virginia Commonwealth University
Phillip B. Hylemon, Virginia Commonwealth UniversityFollow
William M. Pandak Jr., Virginia Commonwealth UniversityFollow
Guangji Wang, Wenzhou Medical College
Xiaokun Li, Wenzhou Medical College
Huiping Zhou, Virginia Commonwealth University, Wenzhou Medical College

Document Type

Article

Original Publication Date

2010

Journal/Book/Conference Title

PLOS ONE

Volume

5

DOI

10.1371/journal.pone.0009069

Comments

Originally Published at http://dx.doi.org/10.1371/journal.pone.0009069

Date of Submission

November 2014

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-α 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-α and IL-6. Berberine significantly inhibited HIV PI-induced TNF-α and IL-6 expression by modulating ER stress signaling pathways and subsequent ERK activation, in turn preventing the accumulation of the RNA binding protein HuR in cytosol and inhibiting the binding of HuR to the 3′-UTRs of TNF-α and IL-6 in macrophages.

Conclusions and Significance

Inhibition of ER stress represents a key mechanism by which berberine prevents HIV PI-induced inflammatory response. Our findings provide a new insight into the molecular mechanisms of berberine and show the potential application of berberine as a complimentary therapeutic agent for HIV infection.

Rights

Copyright: © 2010 Zha et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Is Part Of

VCU Microbiology and Immunology Publications