The Histone Deacetylase Inhibitors MS-275 and SAHA Suppress the p38 Mitogen-Activated Protein Kinase Signaling Pathway and Chemotaxis in Rheumatoid Arthritic Synovial Fibroblastic E11 Cells

Choo, Qiuyi; Ho, Paul C.; Tanaka, Yoshiya; Lin, Hai‐Shu

doi:10.3390/molecules181114085

Cited by 28 publications

(20 citation statements)

References 35 publications

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“…Our previously published data suggest that C3bgp mediated its activity through mitogen-activated protein kinases (MAPK) JNK and p38 18 . Furthermore, our study is in agreement with the work of Choo et al, demonstrating that SAHA suppresses p38 MAPK in synovial fibroblastic E11 cells 19 .…”

Section: Discussionsupporting

confidence: 94%

Suppression of IL-12p40-related regulatory cytokines by suberoylanilide hydroxamic acid an inhibitor of histone deacetylases

Dobreva

Grigorov

Stanilova

2016

Immunopharmacology and Immunotoxicology

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Small molecule inhibitors of histone deacetylases (HDACs) are a new class drugs used in clinical trials for the treatment of various malignancies. Emerging evidence suggest that HDAC inhibitors may also have anti-inflammatory properties, although the molecular mechanisms remain poorly defined. Our study investigates the effect of the HDACs inhibitor suberoylanilide hydroxamic acid (SAHA) on the expression of IL-12p40-related cytokines. For this purpose, human peripheral blood mononuclear cells (PBMC) were stimulated with LPS and C3bgp with or without SAHA. IL-12p40, IL-12p35 and IL-23p19 mRNA was determined at 6 h by qRT-PCR. Cytokine levels were determined in culture supernatants at 6 and 24 h, by ELISA. SAHA significantly inhibited IL-12p40 and IL-23p19 mRNA synthesis and did not change IL-12p35 mRNA transcription. Early at 6 h, we detected significantly decreased IL-12p40 and IL-23, but not IL-12p70 protein production in cultures treated with SAHA. Results also showed that the suppression of IL-12p40-related cytokines was clearly defined at 24 h. However, this suppression was less pronounced regarding IL-12p70. The present study showed that SAHA suppressed the gene expression of IL-23p19 stronger than the expression of IL-12p35, as well as the synthesis of IL-23 compared to that of IL-12p70. We suggest that this inhibitory effect of SAHA may be beneficial during treatment of inflammatory and autoimmune diseases mediated by Th17 immune response.

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Section: Discussionsupporting

confidence: 94%

Suppression of IL-12p40-related regulatory cytokines by suberoylanilide hydroxamic acid an inhibitor of histone deacetylases

Dobreva

Grigorov

Stanilova

2016

Immunopharmacology and Immunotoxicology

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“…The cytokine secretions were measured with ELISA (Choo et al, 2010(Choo et al, , 2013. ELISA sets for human IL-1β, IL-6 and tumor necrosis factor-α (TNF-α) were purchased from BD Biosciences (San Jose, CA 95131, USA).…”

Section: Cytokine Secretionsmentioning

confidence: 99%

“…The impact of stilbenes on monocyte migration was also examined (Choo et al, 2013;Nelson, Quie, & Simmons, 1975).…”

Section: Chemotaxis Assaymentioning

confidence: 99%

Pterostilbene surpassed resveratrol for anti-inflammatory application: Potency consideration and pharmacokinetics perspective

Choo

Yeo

et al. 2014

Journal of Functional Foods

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“…However, recent evidence indicates that HDACs are also involved in the development of inflammatory diseases, highlighting the potential of targeting the activity of HDACs as a therapeutic approach to improve the outcome of rheumatoid arthritis (Choo et al, 2010(Choo et al, , 2013, neuritis (Zhang et al, 2010;Zhang and Schluesener, 2013), cholitis (Felice et al, 2015) and autoimmunity (Hancock et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Class I histone deacetylase inhibition improves pancreatitis outcome by limiting leukocyte recruitment and acinar‐to‐ductal metaplasia

Bombardo

Saponara

Malagola

et al. 2017

British J Pharmacology

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BACKGROUND AND PURPOSEPancreatitis is a common inflammation of the pancreas with rising incidence in many countries. Despite improvements in diagnostic techniques, the disease is associated with high risk of severe morbidity and mortality and there is an urgent need for new therapeutic interventions. In this study, we evaluated whether histone deacetylases (HDACs), key epigenetic regulators of gene transcription, are involved in the development of the disease. EXPERIMENTAL APPROACHWe analysed HDAC regulation during cerulein-induced acute, chronic and autoimmune pancreatitis using different transgenic mouse models. The functional relevance of class I HDACs was tested with the selective inhibitor MS-275 in vivo upon pancreatitis induction and in vitro in activated macrophages and primary acinar cell explants. KEY RESULTSHDAC expression and activity were up-regulated in a time-dependent manner following induction of pancreatitis, with the highest abundance observed for class I HDACs. Class I HDAC inhibition did not prevent the initial acinar cell damage. However, it effectively reduced the infiltration of inflammatory cells, including macrophages and T cells, in both acute and chronic phases of the disease, and directly disrupted macrophage activation. In addition, MS-275 treatment reduced DNA damage in acinar cells and limited acinar de-differentiation into acinar-to-ductal metaplasia in a cell-autonomous manner by impeding the EGF receptor signalling axis. CONCLUSIONS AND IMPLICATIONSThese results demonstrate that class I HDACs are critically involved in the development of acute and chronic forms of pancreatitis and suggest that blockade of class I HDAC isoforms is a promising target to improve the outcome of the disease. IntroductionAbnormal activity of histone deacetylases (HDACs), a family of enzymes involved in the epigenetic control of gene transcription, has been implicated in the aetiology and development of several malignancies. However, recent evidence indicates that HDACs are also involved in the development of inflammatory diseases, highlighting the potential of targeting the activity of HDACs as a therapeutic approach to improve the outcome of rheumatoid arthritis (Choo et al., 2010(Choo et al., , 2013, neuritis (Zhang et al., 2010;Zhang and Schluesener, 2013), cholitis (Felice et al., 2015) and autoimmunity (Hancock et al., 2012).HDACs control the acetylation status of histone and non-histone proteins, thus regulating the expression of target genes (reviewed in Delcuve et al., 2012). The complexity of acetylation-based epigenetic regulation is reflected by the size of the mammalian HDAC family, composed of 11 zinc-dependent enzymes divided into three subfamilies (classes I, II and IV) and seven NAD-dependent enzymes in a fourth (sirtuin) subfamily (class III), with non-redundant functions.The function of HDAC subfamilies in the pathophysiology of pancreatitis, a highly debilitating inflammatory disease with a potentially lethal outcome, has not been thoroughly investigated. During pancreatitis, the ...

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The Histone Deacetylase Inhibitors MS-275 and SAHA Suppress the p38 Mitogen-Activated Protein Kinase Signaling Pathway and Chemotaxis in Rheumatoid Arthritic Synovial Fibroblastic E11 Cells

Cited by 28 publications

References 35 publications

Suppression of IL-12p40-related regulatory cytokines by suberoylanilide hydroxamic acid an inhibitor of histone deacetylases

Suppression of IL-12p40-related regulatory cytokines by suberoylanilide hydroxamic acid an inhibitor of histone deacetylases

Pterostilbene surpassed resveratrol for anti-inflammatory application: Potency consideration and pharmacokinetics perspective

Class I histone deacetylase inhibition improves pancreatitis outcome by limiting leukocyte recruitment and acinar‐to‐ductal metaplasia

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