Hindsiipropane B alleviates HIV-1 Tat-induced inflammatory responses by suppressing HDAC6-NADPH oxidase-ROS axis in astrocytes
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초록
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. 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.
Abstract
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. 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.
참고문헌 (27)
- Yao H, "HIV neuropathogenesis: a tight rope walk of innate immunity", J Neuroimmune Pharmacol, 5, pp.489~495 (2010)[DOI]
- Ozdener H, "Molecular mechanisms of HIV-1 associated neurodegeneration", J Biosci, 30, pp.391~405 (2005)[DOI]
- Nookala AR, "Molecular mechanisms involved in HIV-1 Tat-mediated induction of IL-6 and IL-8 in astrocytes", J Neuroinflammation, 11, pp.214~ (2014)[DOI]
- Youn GS, "Celastrol ameliorates HIV-1 Tat-induced inflammatory responses via NF-kappaB and AP-1 inhibition and heme oxygenase-1 induction in astrocytes", Toxicol Appl Pharmacol, 280, pp.42~52 (2014)[DOI]
- Farina C, "Astrocytes are active players in cerebral innate immunity", Trends Immunol, 28, pp.138~145 (2007)[DOI]
- Bagashev A, "Roles and functions of HIV-1 Tat protein in the CNS: an overview", Virol J, 10, pp.358~ (2013)[DOI]
- Youn GS, "HDAC6 mediates HIV-1 tat-induced proinflammatory responses by regulating MAPK-NF-kappaB", AP-1 pathways in astrocytes, 2015, pp.63, 1953~1965
- Youn GS, "Crosstalk between HDAC6 and Nox2-based NADPH oxidase mediates HIV-1 Tat-induced pro-inflammatory responses in astrocytes", Redox Biol, 12, pp.978~986 (2017)[DOI]
- Lambeth JD, "Regulation of Nox and Duox enzymatic activity and expression", Free Radic Biol Med, 43, pp.319~331 (2007)[DOI]
- Bruce-Keller AJ, "Pro-inflammatory and pro-oxidant properties of the HIV protein Tat in a microglial cell line: attenuation by 17 beta-estradiol", J Neurochem, 78, pp.1315~1324 (2001)[DOI]
- Lim SP, "The human immunodeficiency virus type 1 Tat protein up-regulates the promoter activity of the beta-chemokine monocyte chemoattractant protein 1 in the human astrocytoma cell line U-87 MG: role of SP-1, AP-1, and NF-kappaB consensus sites", J Virol, 74, pp.1632~1640 (2000)[DOI]
- Song HY, "Nox2-based NADPH oxidase mediates HIV-1 Tat-induced up-regulation of VCAM-1", ICAM-1 and subsequent monocyte adhesion in human astrocytes, 2011, pp.50, 576~584
- Xian Qing Hu, "Three new diphenylpropanes from Celastrus hindsii", Archives of Pharmacal Research, 37(11), pp.1411~1415 (2014), 대한약학회
- Jang HY, "Dihydrostilbenes and diarylpropanes: Synthesis and in vitro pharmacological evaluation as potent nitric oxide production inhibition agents", Bioorg Med Chem Lett, 26, pp.5438~5443 (2016)[DOI]
- Vijaya Bhaskar Reddy M, "Synthesis and biological evaluation of chalcone, dihydrochalcone, and 1,3-diarylpropane analogs as antiinflammatory agents", Bioorg Med Chem Lett, 27, pp.1547~1550 (2017)[DOI]
- Li JC, "Role of HIV-1 Tat in AIDS pathogenesis: its effects on cytokine dysregulation and contributions to the pathogenesis of opportunistic infection", AIDS, 24, pp.1609~1623 (2010)[DOI]
- Rappaport J, "Molecular pathway involved in HIV-1-induced CNS pathology: role of viral regulatory protein, Tat", J Leukoc Biol, 65, pp.458~465 (1999)[DOI]
- Youn GS, "Overexpression of HDAC6 induces pro-inflammatory responses by regulating ROS-MAPK-NF-kappaB", AP-1 signaling pathways in macrophages, 2016, pp.97, 14~23
- Abramov AY, "Expression and modulation of an NADPH oxidase in mammalian astrocytes", J Neurosci, 25, pp.9176~9184 (2005)[DOI]
- Brown DI, "Nox proteins in signal transduction", Free Radic Biol Med, 47, pp.1239~1253 (2009)[DOI]
- Gloire G, "NF-kappaB activation by reactive oxygen species: fifteen years later", Biochem Pharmacol, 72, pp.1493~1505 (2006)[DOI]
- 주성미, "Extracellular HIV-1 Tat up-regulates expression of matrix metalloproteinase-9 via a MAPK-NF-κB dependent pathway in human astrocytes", Experimental and Molecular Medicine, 41(2), pp.86~93 (2009), 생화학분자생물학회
- Kutsch O, "Induction of the chemokines interleukin-8 and IP-10 by human immunodeficiency virus type 1 tat in astrocytes", J Virol, 74, pp.9214~9221 (2000)[DOI]
- 안수연, "Celastrol suppresses expression of adhesion molecules and chemokines by inhibiting JNK-STAT1", NF-κB activation in poly(I:C)-stimulated astrocytes, 2017, pp.50(1), 25~30[DOI]
- Herrmann CH, "Specific interaction of the human immunodeficiency virus Tat proteins with a cellular protein kinase", Virology, 197, pp.601~608 (1993)[DOI]
- 조효상, "Effects of PEP-1-FK506BP on cyst formation in polycystic kidney disease", BMB Reports, 50(9), pp.460~465 (2017), 생화학분자생물학회
- Yaojin Peng, "Tubeimoside-1 suppresses breast cancer metastasis through downregulation of CXCR4 chemokine receptor expression", BMB Reports, 49(9), pp.502~507 (2016), 생화학분자생물학회