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

Autor: Dobreva ZG; a Department of Molecular Biology, Immunology and Medical Genetics, Medical Faculty , Trakia University , Bulgaria., Grigorov BG; a Department of Molecular Biology, Immunology and Medical Genetics, Medical Faculty , Trakia University , Bulgaria., Stanilova SA; a Department of Molecular Biology, Immunology and Medical Genetics, Medical Faculty , Trakia University , Bulgaria.
Jazyk: angličtina
Zdroj: Immunopharmacology and immunotoxicology [Immunopharmacol Immunotoxicol] 2016 Aug; Vol. 38 (4), pp. 281-5. Date of Electronic Publication: 2016 May 31.
DOI: 10.1080/08923973.2016.1188940
Abstrakt: 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.
Databáze: MEDLINE
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