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

• Published in: BMB reports Vol. 51; no. 8; pp. 394 - 399
• Main Authors: Jo, Hyundong, Jang, Ha Young, Youn, Gi Soo, Kim, Donggyu, Lee, Chae Yeon, Jang, Jae Hee, Choi, Soo Young, Jun, Jong-Gab, Park, Jinseu
• Format: Journal Article
• Language: English
• Published: Korea (South) Korean Society for Biochemistry and Molecular Biology 01.08.2018; 생화학분자생물학회
• Subjects: Astrocytes - drug effects; Astrocytes - metabolism; Astrocytes - pathology; Astrocytes - virology; Celastrus - chemistry; Cell Line; Chemokines - biosynthesis; Chemokines - immunology; Histone Deacetylase 6 - antagonists & inhibitors; Histone Deacetylase 6 - metabolism; HIV Infections - drug therapy; HIV Infections - immunology; HIV Infections - metabolism; HIV-1 - metabolism; Humans; Inflammation - immunology; Inflammation - virology; MAP Kinase Signaling System - drug effects; NADPH Oxidases - antagonists & inhibitors; NADPH Oxidases - metabolism; NF-kappa B - metabolism; Plant Extracts - pharmacology; Propane - analogs & derivatives; Propane - pharmacology; Proto-Oncogene Proteins c-akt - metabolism; Reactive Oxygen Species - antagonists & inhibitors; Reactive Oxygen Species - metabolism; tat Gene Products, Human Immunodeficiency Virus - immunology; tat Gene Products, Human Immunodeficiency Virus - metabolism; 화학
• ISSN: 1976-6696; 1976-670X
• DOI: 10.5483/BMBRep.2018.51.8.061

Human immunodeficiency virus-1 (HIV-1) transactivator of transcription (Tat) is an important viral factor in neuroinflammation. Hindsiipropane B, present in Celastrus hindsii, possesses various biological mechanisms including antiinflammatory 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-κB, 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 oxidase-MAPK-NF-κB/AP-1 signaling axis, and could serve as a therapeutic lead compound against HIV-1 Tat-associated neuroinflammation. [BMB Reports 2018; 51(8): 394-399].