Vorinostat, a histone deacetylase inhibitor, suppresses dendritic cell function and ameliorates experimental autoimmune encephalomyelitis

Zhang, Ge; Da, Yurong; Xue, Zhenyi; Zhang, Kai; Zhuang, Hao; Peng, Meiyu; Li, Yan; Wen, Li; Simard, Alain R.; Hao, Junwei; Yao, Zhi; Zhang, Rongxin

doi:10.1016/j.expneurol.2012.12.006

Cited by 83 publications

(52 citation statements)

References 53 publications

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“…Similar results were reported by other authors 2,4,11,13,16 . Regardless of the stimuli used, the inhibitory effect of SAHA was powerful and occurred rapidly -reduced IL-12p40 and IL-23 mRNA and protein was detected in cultures treated with SAHA, early at 6 h after stimulation.…”

Section: Discussionsupporting

confidence: 93%

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: 93%

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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show abstract

“…Similar results regarding IL-12p40 and IL-23 at mRNA and protein level were reported by other authors (3,5,7,13,16). Regardless of the stimuli used, the inhibitory effect of SAHA was powerful and was occurred rapidly -reduced quantity of IL-12p40 and IL-23 was detected in cultures treated with SAHA, early at 6h.…”

Section: Discussionsupporting

confidence: 88%

Suppression of proinflammatory cytokine production by suberoylanilide hydroxamic acid an inhibitor of histone deacetylases

Dobreva¹,

Stanilova²

2015

TJS

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ABSRACTChromatin remodeling by acetylation and deacetylation of histones play an essential role in regulation of the gene expression. The opposing activity of two type enzymes controls the acetylation degree of the chromatin structure. Histone acetylation by acetyltransferases leads to relaxed chromatin structure and this process supports the transcription. Deacetylation by histone deacetylases (HDACs) compact the chromatin structure and favors gene silence. Small molecule inhibitors of HDACs are a new class drugs used in clinical trials for the treatment of various malignancies. Emerging evidence suggest that HDAC inhibitors may have also anti-inflammatory properties, although the molecular mechanisms remain poorly defined. Our study investigates the effect of the HDACs inhibitor Suberoylanilide Hydroxamic Acid (SAHA) on Th1 and Th17 polarizing cytokines IL-12p40 and IL-23. For this purpose, human peripheral blood mononuclear cells (PBMC) were stimulated with LPS and C3bgp with or without SAHA. Cytokine production was determined in culture supernatants at 6 and 24 h, by ELISA. IL-12p40 and IL-23 synthesis was measured in stimulated PBMC at 6 and increased at 24 h. Early at 6 h, we detected significantly decreased IL-12p40 and IL-23 production in stimulated PBMC treated with SAHA and this tendency was retained at 24 h. In conclusion, our results demonstrated that the inhibition of HDACs by SAHA leads to suppression of IL-12p40 and IL-23 regardless of stimuli used. The downregulating effect of SAHA on the proinflammatory cytokine production may be beneficial during treatment of chronic inflammatory diseases which progression is mediated by Th17 immune response.

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“…These data are in line with previous reports showing antiinflammatory actions of HDACi. More specifically, SAHA was found to mediate antiinflammatory actions in various models of inflammation, such as corneal neovascularization (86), sepsis (87), intrapulmonary inflammation (88), and encephalomyelitis (89). Of note, neither in our aging nor in the amyloid model was increased expression of inflammatory genes associated with elevated H4K12ac in nonneuronal cells.…”

Section: Discussionmentioning

confidence: 93%

HDAC inhibitor–dependent transcriptome and memory reinstatement in cognitive decline models

Benito

Urbanke

Ramachandran

et al. 2015

Journal of Clinical Investigation

161

137

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Vorinostat, a histone deacetylase inhibitor, suppresses dendritic cell function and ameliorates experimental autoimmune encephalomyelitis

Cited by 83 publications

References 53 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

Suppression of proinflammatory cytokine production by suberoylanilide hydroxamic acid an inhibitor of histone deacetylases

HDAC inhibitor–dependent transcriptome and memory reinstatement in cognitive decline models

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