Effect of a Histone Deacetylases Inhibitor of IL-18 and TNF-Alpha Secretion in Vitro
BACKGROUND: Interleukin-18 (IL-18) and Tumor Necrosis Factor-alpha (TNF-Î±) are proinflammatory cytokines that increased the development of Th1 immune response, but have a different type of regulation of the gene expression. Whereas TNF-Î± 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-Î±, 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-Î± secretion was significantly increased at 6h and 24h in response to stimulation. TNF-Î± 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-Î± in cultures was mediated by the activity of HDAC class I and class II enzymes.
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