PMID- 29531586 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201001 IS - 1857-9655 (Print) IS - 1857-9655 (Electronic) IS - 1857-9655 (Linking) VI - 6 IP - 2 DP - 2018 Feb 15 TI - Effect of a Histone Deacetylases Inhibitor of IL-18 and TNF-Alpha Secretion in Vitro. PG - 269-273 LID - 10.3889/oamjms.2018.075 [doi] AB - BACKGROUND: Interleukin-18 (IL-18) and Tumor Necrosis Factor-alpha (TNF-alpha) are proinflammatory cytokines that increased the development of Th1 immune response, but have a different type of regulation of the gene expression. Whereas TNF-alpha 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-alpha, 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-alpha secretion was significantly increased at 6h and 24h in response to stimulation. TNF-alpha 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-alpha in cultures was mediated by the activity of HDAC class I and class II enzymes. FAU - Dobreva, Zlatka Georgieva AU - Dobreva ZG AD - Department of Molecular Biology, Immunology and Medical Genetics, Medical Faculty, Trakia University, Armeiska 11, Stara Zagora 6000, Bulgaria. FAU - Grigorov, Boncho Grigorov AU - Grigorov BG AD - Department of Molecular Biology, Immunology and Medical Genetics, Medical Faculty, Trakia University, Armeiska 11, Stara Zagora 6000, Bulgaria. FAU - Stanilova, Spaska Angelova AU - Stanilova SA AD - Department of Molecular Biology, Immunology and Medical Genetics, Medical Faculty, Trakia University, Armeiska 11, Stara Zagora 6000, Bulgaria. LA - eng PT - Journal Article DEP - 20180210 PL - North Macedonia TA - Open Access Maced J Med Sci JT - Open access Macedonian journal of medical sciences JID - 101662294 PMC - PMC5839430 OTO - NOTNLM OT - HDAC OT - IL-18 OT - PBMC OT - SAHA OT - TNF-alpha EDAT- 2018/03/14 06:00 MHDA- 2018/03/14 06:01 PMCR- 2018/02/10 CRDT- 2018/03/14 06:00 PHST- 2017/11/20 00:00 [received] PHST- 2017/12/04 00:00 [revised] PHST- 2017/12/05 00:00 [accepted] PHST- 2018/03/14 06:00 [entrez] PHST- 2018/03/14 06:00 [pubmed] PHST- 2018/03/14 06:01 [medline] PHST- 2018/02/10 00:00 [pmc-release] AID - OAMJMS-6-269 [pii] AID - 10.3889/oamjms.2018.075 [doi] PST - epublish SO - Open Access Maced J Med Sci. 2018 Feb 10;6(2):269-273. doi: 10.3889/oamjms.2018.075. eCollection 2018 Feb 15.