Abstract
Histones are basic proteins that wrap around DNA for conditional accessibility of DNA to their transcription; however, HDAC6 is a unique histone deacetylase capable of deacetylating both histone and non-histone proteins. Recently HDAC6 has been shown to play an inflammatory role by limiting p38-MAPK activation in an LPS sepsis model. Here, we tested the ability of HDAC6 inhibition to control inflammation initiated by B. burgdorferi both in vitro and in vivo. The data indicate inhibition of HDAC6 leads to an increase in pro-inflammatory cytokines in macrophages and mice. HDAC6 deficient macrophages revealed similar results when co-incubated with B. burgdorferi. Inhibition of HDAC6 also resulted in diverse responses when exposed to different TLR ligands, suggesting a more complex role of HDAC6 in the inflammatory process. Additionally, inhibition of HDAC6 led to an increased acetylation of tubulin; however, there was minimal impact on p38-MAPK phosphorylation.
Keywords: HDAC6; Tubastatin A; Borrelia; Inflammation; TLR
References
- Radolf JD., et al. “Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes”. Nature Reviews Microbiology 2 (2012): 87-99.
- Lasky CE., et al. “Macrophage Polarization during Murine Lyme Borreliosis”. Infection and Immunity 7 (2015): 2627-2635.
- Sonderegger FL., et al. “Localized production of IL-10 suppresses early inflammatory cell infiltration and subsequent development of IFN-gamma-mediated Lyme arthritis”. Journal of Immunology 3 (2012): 1381-1393.
- Sahay B., et al. “CD14 signaling restrains chronic inflammation through induction of p38-MAPK/SOCS-dependent tolerance”. PLOS Pathogens 12 (2009): e1000687.
- Li Y., et al. “Inhibition of histone deacetylase 6 improves long-term survival in a lethal septic model”. The Journal of Trauma and Acute Care Surgery2 (2015): 378-385.
- Yan B., et al. “HDAC6 deacetylase activity is critical for lipopolysaccharide-induced activation of macrophages”. PLoS One10 (2014): e110718.
- Wang B., et al. “Microtubule acetylation amplifies p38 kinase signalling and anti-inflammatory IL-10 production”. Nature Communications 5 (2014): 3479.
- Hawley K., et al. “Macrophage p38 mitogen-activated protein kinase activity regulates invariant natural killer T-cell responses during Borrelia burgdorferi infection”. The Journal of Infectious Diseases 2 (2012): 283-291.
- Sahay B., et al. “Induction of Interleukin 10 by Borrelia burgdorferi Is Regulated by the Action of CD14-Dependent p38 Mitogen-Activated Protein Kinase and cAMP-Mediated Chromatin Remodeling”. Infection and Immunity 4 (2018): e00781.
- Hubbert C., et al. “HDAC6 is a microtubule-associated deacetylase”. Nature6887 (2002): 455-458.
- Crandall H., et al. “Gene expression profiling reveals unique pathways associated with differential severity of lyme arthritis”. Journal of Immunology 11 (2006): 7930-7942.
- Li Y., et al. “Histone deacetylase 6 plays a role as a distinct regulator of diverse cellular processes”. The FEBS Journal 3 (2013): 775-793.
- Bertos NR., et al. “Role of the tetradecapeptide repeat domain of human histone deacetylase 6 in cytoplasmic retention”. Journal of Biological Chemistry 46 (2004): 48246-48254.
- Verdel A., et al. “Active maintenance of mHDA2/mHDAC6 histone-deacetylase in the cytoplasm”. Current Biology: CB 12 (2000): 747-749.
- Boyault C., et al. “HDAC6-p97/VCP controlled polyubiquitin chain turnover”. The EMBO Journal 14 (2006): 3357-3366.
- Liu Y., et al. “Modulation of histone deacetylase 6 (HDAC6) nuclear import and tubulin deacetylase activity through acetylation”. Journal of Biological Chemistry 34 (2012): 29168-29174.
- Fusco C., et al. “The E3-ubiquitin ligase TRIM50 interacts with HDAC6 and p62, and promotes the sequestration and clearance of ubiquitinated proteins into the aggresome”. PLoS One7 (2012): e40440.
- Cheng F., et al. “A novel role for histone deacetylase 6 in the regulation of the tolerogenic STAT3/IL-10 pathway in APCs”. Journal of Immunology 6 (2014): 2850-2862.
- Villagra A., et al. “The histone deacetylase HDAC11 regulates the expression of interleukin 10 and immune tolerance”. Nature Immunology 1 (2009): 92-100.
- Cheng F., et al. “Divergent roles of histone deacetylase 6 (HDAC6) and histone deacetylase 11 (HDAC11) on the transcriptional regulation of IL10 in antigen presenting cells”. Molecular Immunology1 (2014): 44-53.
- Zenk SF., et al. “Role of <em>Salmonella enterica</em> Lipopolysaccharide in Activation of Dendritic Cell Functions and Bacterial Containment”. The Journal of Immunology 4 (2009): 2697-2707.
- Pupo E., et al. “Intact rough- and smooth-form lipopolysaccharides from Escherichia coli separated by preparative gel electrophoresis exhibit differential biologic activity in human macrophages”. The FEBS Journal 4 (2013): 1095-1111.
- Rittig MG., et al. “Smooth and rough lipopolysaccharide phenotypes of Brucella induce different intracellular trafficking and cytokine/chemokine release in human monocytes”. Journal of Leukocyte Biology 6 (2003): 1045-1055.
- Godowski PJ. “A smooth operator for LPS responses”. Nature Immunology 6 (2005): 544-546.
- YL Lightfoot., et al. “Colonic Immune Suppression, Barrier Dysfunction, and Dysbiosis by Gastrointestinal Bacillus anthracis Infection”. PLoS One 9 (2014): e100532.
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