Control of cytokine mRNA degradation by the histone deacetylase inhibitor ITF2357 in rheumatoid arthritis fibroblast-like synoviocytes: beyond transcriptional regulation

Abstract

ITF2357 leads to TTP transcriptional and post-translational changes Early studies in cancer cells indicated that HDACi modulate ARE-BP function [28, 29]. [...]we investigated the expression of both destabilizing (TTP, AUF1, BRF1, BRF2, KHRSP) and stabilizing (HuR) ARE-BP after short treatment with ITF2357 in RA FLS. Phosphorylation is the most common post-translational modification of TTP and other ARE-BP, but other modifications have been reported [45, 46]. [...]it remains possible that ITF2357 may enhance the acetylation levels of TTP and subsequently reduce its phosphorylation. [...]evidence from the literature suggests that HDAC1,2 and 3 can bind to and acetylate Dusp1 [47]. (PDF 111 kb) Authors’ Affiliations (1) Laboratory of Translational Immunology and Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands (2) Amsterdam Rheumatology and Immunology Center, Department of Clinical Immunology and Rheumatology and Department of Experimental Immunology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands (3) Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland (4) Functional Genomics Center, University of Verona, Verona, Italy (5) Signal Transduction Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA (6) Italfarmaco Research and Development, Cinisello Balsamo, Italy Smolen JS, Aletaha D, Mcinnes IB.