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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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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)
  • Received : 2018.03.23
  • Accepted : 2018.04.23
  • Published : 2018.08.31
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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.

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References

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