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Rosiglitazone suppresses HIV-1 Tat-induced vascular inflammation via Akt signaling

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Abstract

Peroxisome proliferator-activated receptor gamma (PPARƔ) contributes to human immunodeficiency virus (HIV)-1-induced dysfunction of brain endothelial cells. The aim of the present study was to evaluate the protection mechanism of PPARƔ against Tat-induced responses of adhesion molecules. We measured the protein expressions of intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 in human brain microvascular endothelial cells (hCMEC/D3) and C57BL/6J mouse brain microvessels with Western blotting and immunofluorescent labeling. The mRNA levels of ICAM-1 and VCAM-1 were determined by real-time reverse-transcriptase polymerase chain reaction. HIV-1 Tat induced overexpression of ICAM-1 but not VCAM-1 in both hCMEC/D3 and brain microvessels, this response was attenuated by treatment with the PPARƔ agonist rosiglitazone. Tat-mediated upregulation of ICAM-1 and VCAM-1 levels were abolished by the addition of PPARƔ antagonist GW9662 and the Akt inhibitor KP3721, indicating that Akt signaling is involved in the PPARƔ-mediated protection of Tat-induced adhesion molecule upregulation. These results show that Akt signaling plays a key role in PPARƔ’s vascular inflammatory effects that contribute to blood–brain barrier damage.

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Acknowledgments

This work was supported by the National Nature Science Foundation of China (81160152, 81371333, 81360057) and Guangxi Nature Science Foundation (2013GXNSFCA019013, 2013GXNSFAA019184).

Conflict of interest

The authors have nothing to disclose.

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Authors and Affiliations

  1. Department of Neurology, First Affiliated Hospital, Guangxi Medical University, Nanning, 530021, People’s Republic of China

    Wen Huang, Wenjing Luo & Yanlan Chen

  2. School of Nursing, First Affiliated Hospital, Guangxi Medical University, Nanning, 530021, People’s Republic of China

    Xuean Mo

  3. Department of Vasculocardiology, First Affiliated Hospital, Guangxi Medical University, #6 Shuangyong Road, Nanning, 530021, Guangxi, People’s Republic of China

    Xianghong Wu

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  1. Wen Huang
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Correspondence to Xianghong Wu.

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Huang, W., Mo, X., Wu, X. et al. Rosiglitazone suppresses HIV-1 Tat-induced vascular inflammation via Akt signaling. Mol Cell Biochem 407, 173–179 (2015). https://doi.org/10.1007/s11010-015-2467-2

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  • DOI: https://doi.org/10.1007/s11010-015-2467-2

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