Effect of a Histone Deacetylases Inhibitor of IL-18 and TNF-Alpha Secretion in Vitro

  • Zlatka Georgieva Dobreva Department of Molecular Biology, Immunology and Medical Genetics, Medical Faculty, Trakia University, Armeiska 11, Stara Zagora 6000
  • Boncho Grigorov Grigorov Department of Molecular Biology, Immunology and Medical Genetics, Medical Faculty, Trakia University, Armeiska 11, Stara Zagora 6000
  • Spaska Angelova Stanilova Department of Molecular Biology, Immunology and Medical Genetics, Medical Faculty, Trakia University, Armeiska 11, Stara Zagora 6000
Keywords: HDAC, IL-18, SAHA, TNF-α, PBMC

Abstract

BACKGROUND: Interleukin-18 (IL-18) and Tumor Necrosis Factor-alpha (TNF-α) are proinflammatory cytokines that increased the development of Th1 immune response, but have a different type of regulation of the gene expression. Whereas TNF-α has an inducible expression, IL-18 is translated as an inactive protein and required proteolytic cleavage by Casp-1 in inflammasome complexes.

AIM: To investigate the effect of the histone deacetylases inhibitor Suberoylanilide Hydroxamic Acid (SAHA) on the gene expression and secretion of both cytokines, IL-18 and TNF-α, according to their contribution to the cancer development and anticancer immunity.

METHODS: Isolated peripheral blood mononuclear cells (PBMC) were stimulated with LPS and C3bgp with or without SAHA. Cytokine production was assessed by ELISA at 6 and 24h.

RESULTS: IL-18 and TNF-α secretion was significantly increased at 6h and 24h in response to stimulation. TNF-α production from stimulated PBMC was downregulated by SAHA at 6 and 24h. Treatment with SAHA does not inhibit the secretion of IL-18 significantly either at 6 or 24h of stimulation.

CONCLUSION: The inhibition of histone deacetylases by SAHA does not influence the inflammasome-dependent production of immunologically active IL-18. In contrast, the production of proinflammatory TNF-α in cultures was mediated by the activity of HDAC class I and class II enzymes.

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Published
2018-02-10
How to Cite
1.
Dobreva ZG, Grigorov BG, Stanilova SA. Effect of a Histone Deacetylases Inhibitor of IL-18 and TNF-Alpha Secretion in Vitro. Open Access Maced J Med Sci [Internet]. 2018Feb.10 [cited 2020Nov.25];6(2):269-73. Available from: https://www.id-press.eu/mjms/article/view/oamjms.2018.075
Section
A - Basic Science