Crosstalk between HDAC6 and Nox2-based NADPH oxidase mediates HIV-1 Tat-induced pro-inflammatory responses in astrocytes

Histone deacetylase 6 (HDAC6) likely is important in inflammatory diseases. However, how HDAC6 exerts its effect on inflammatory processes remains unclear. HIV-1 transactivator of transcription (Tat) activates NADPH oxidase resulting in generation of reactive oxygen species (ROS), leading to extensi...

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Bibliographic Details
Published in:Redox biology 2017-08, Vol.12, p.978-986
Main Authors: Youn, Gi Soo, Cho, Hyundong, Kim, Donggyu, Choi, Soo Young, Park, Jinseu
Format: Article
Language:English
Subjects:
Animals
Astrocytes - cytology
Astrocytes - drug effects
Astrocytes - immunology
Astrocytes - virology
Cell Line
Chemokines - genetics
Chemokines - metabolism
Gene Knockdown Techniques
Histone Deacetylase 6 - genetics
Histone Deacetylase 6 - metabolism
HIV-1 - immunology
HIV-1 - metabolism
Humans
Hydroxamic Acids - pharmacology
Indoles - pharmacology
Mice
NADPH Oxidase 2 - genetics
NADPH Oxidase 2 - metabolism
Reactive Oxygen Species - metabolism
Research Paper
tat Gene Products, Human Immunodeficiency Virus - immunology
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Summary:Histone deacetylase 6 (HDAC6) likely is important in inflammatory diseases. However, how HDAC6 exerts its effect on inflammatory processes remains unclear. HIV-1 transactivator of transcription (Tat) activates NADPH oxidase resulting in generation of reactive oxygen species (ROS), leading to extensive neuro-inflammation in the central nervous system. We investigated the correlation of HDAC6 and NADPH oxidase in HIV-1 Tat-stimulated astrocytes. HDAC6 knockdown attenuated HIV-1 Tat-induced ROS generation and NADPH oxidase activation. HDAC6 knockdown suppressed HIV-1 Tat-induced expression of NADPH oxidase subunits, such as Nox2, p47phox, and p22phox. Specific inhibition of HDAC6 using tubastatin A suppressed HIV-1 Tat-induced ROS generation and activation of NADPH oxidase. N-acetyl cysteine, diphenyl iodonium, and apocynin suppressed HIV-1 Tat-induced expression of HDAC6 and the pro-inflammatory chemokines CCL2, CXCL8, and CXCL10. Nox2 knockdown attenuated HIV-1 Tat-induced HDAC6 expression and subsequent expression of chemokines. The collective results point to the potential crosstalk between HDAC6 and NADPH oxidase, which could be a combined therapeutic target for relief of HIV-1 Tat-mediated neuro-inflammation.
ISSN:2213-2317
2213-2317
DOI:10.1016/j.redox.2017.05.001