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HDAC6 regulates LPS-tolerance in astrocytes.
1Department of Psychiatry and Behavioral Sciences, University of Miami, Miami, Florida, United States of America. eleonore_beurel@hotmail.fr
Plos One
|October 25, 2011
Summary
Neuroinflammation can be controlled by inflammatory tolerance. This study reveals that histone deacetylase 6 (HDAC6) promotes tolerance, while glycogen synthase kinase-3 (GSK3) counteracts it, offering new therapeutic targets.
Area of Science:
- Neuroscience
- Immunology
- Molecular Biology
Background:
- Chronic inflammation in the central nervous system contributes to neurodegenerative and psychiatric diseases.
- Existing inflammatory tolerance mechanisms are often insufficient to control neuroinflammation.
Purpose of the Study:
- To identify regulatory mechanisms of neuroinflammatory tolerance.
- To explore potential strategies for enhancing tolerance to reduce chronic neuroinflammation.
Main Methods:
- Investigated inflammatory tolerance using repeated lipopolysaccharide (LPS) stimulation in mouse primary astrocytes.
- Examined the roles of histone deacetylase (HDAC) activity and glycogen synthase kinase-3 (GSK3) in modulating LPS tolerance.
- Utilized the HDAC6 inhibitor tubacin to assess its impact on tolerance.
Main Results:
- HDAC activity promoted LPS tolerance, while GSK3 counteracted it.
- HDAC6 was critical for tolerance induction, evidenced by increased deacetylation of acetyl-tubulin during LPS tolerance.
- Inhibition of GSK3 enhanced HDAC6-mediated tolerance, whereas the HDAC6 inhibitor tubacin blocked tolerance and GSK3 inhibition's pro-tolerance effects.
Conclusions:
- HDAC6 and GSK3 have opposing roles in regulating inflammatory tolerance in astrocytes.
- Modulating the balance between HDAC6 and GSK3 activity can significantly impact LPS tolerance, offering potential therapeutic avenues for neuroinflammatory diseases.
