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http://dx.doi.org/10.5483/BMBRep.2018.51.8.061

Hindsiipropane B alleviates HIV-1 Tat-induced inflammatory responses by suppressing HDAC6-NADPH oxidase-ROS axis in astrocytes  

Jo, Hyundong (Department of Biomedical Science and Research Institute for Bioscience & Biotechnology, Hallym University)
Jang, Ha Young (Department of Chemistry and Institute of Applied Chemistry, Hallym University)
Youn, Gi Soo (Department of Biomedical Science and Research Institute for Bioscience & Biotechnology, Hallym University)
Kim, Donggyu (Department of Biomedical Science and Research Institute for Bioscience & Biotechnology, Hallym University)
Lee, Chae Yeon (Department of Biomedical Science and Research Institute for Bioscience & Biotechnology, Hallym University)
Jang, Jae Hee (Department of Biomedical Science and Research Institute for Bioscience & Biotechnology, Hallym University)
Choi, Soo Young (Department of Biomedical Science and Research Institute for Bioscience & Biotechnology, Hallym University)
Jun, Jong-Gab (Department of Chemistry and Institute of Applied Chemistry, Hallym University)
Park, Jinseu (Department of Biomedical Science and Research Institute for Bioscience & Biotechnology, Hallym University)
Publication Information
BMB Reports / v.51, no.8, 2018 , pp. 394-399 More about this Journal
Abstract
Human immunodeficiency virus-1 (HIV-1) transactivator of transcription (Tat) is an important viral factor in neuro-inflammation. Hindsiipropane B, present in Celastrus hindsii, possesses various biological mechanisms including anti-inflammatory activity. In this report, we explored the regulatory activity of hindsiipropane B on HIV-1 Tat-mediated chemokine production and its mode of action in astrocytes. Hindsiipropane B significantly alleviated HIV-1 Tat-mediated production of inflammatory chemokines, CCL2, CXCL8, and CXCL10. Hindsiipropane B inhibited expression of HDAC6, which is important regulator in HIV-1 Tat-mediated chemokine production. Hindsiipropane B diminished HIV-1 Tat-mediated reactive oxygen species (ROS) generation and NADPH oxidase activation/expression. Furthermore, hindsiipropane B inhibited HIV-1 Tat-mediated signaling cascades including MAPK, $NF-{\kappa}B$, and AP-1. These data suggest that hindsiipropane B exerts its inhibitory effects on HIV-1 Tat-mediated chemokine production via down-regulating the HDAC6-NADPH oxidaseMAPK-$NF-{\kappa}B$/AP-1 signaling axis, and could serve as a therapeutic lead compound against HIV-1 Tat-associated neuro-inflammation.
Keywords
Chemokines; HDAC6; HIV-1 Tat; Inflammation; NADPH oxidase;
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