Abstract
SIRT1, a class III histone/protein deacetylase (HDAC), has been associated with autoimmune diseases. There is a paucity of data about the role of SIRT1 in Graves’ disease. The aim of this study was to investigate the role of SIRT1 in the pathogenesis of GD. Here, we showed that SIRT1 expression and activity were significantly decreased in GD patients compared with healthy controls. The NF-κB pathway was activated in the peripheral blood of GD patients. The reduced SIRT1 levels correlated strongly with clinical parameters. In euthyroid patients, SIRT1 expression was markedly upregulated and NF-κB downstream target gene expression was significantly reduced. SIRT1 inhibited the NF-κB pathway activity by deacetylating P65. These results demonstrate that reduced SIRT1 expression and activity contribute to the activation of the NF-κB pathway and may be involved in the pathogenesis of GD.
Highlights
Graves’ disease (GD) is the most common cause of hyperthyroidism, in which patients develop an antithyroid autoimmune response, including lymphocytic infiltration and the presence of autoantibodies against thyroglobulin, thyroid peroxidase and the thyroidstimulating hormone receptor (TSHR) (Weetman 2000)
To investigate whether SIRT1 is involved in the pathogenesis of GD, we first measured whether SIRT1 was positive in CD4+ T, CD8+T, B-lymphocytes and monocytes which were the main composition of peripheral blood mononuclear cells (PBMCs), and we found SIRT1 was positive in them all (Supplementary Fig. 1)
SIRT1 protein levels in PBMCs were reduced in GD patients compared to healthy controls (HCs) (Fig. 1B), which was further confirmed by immunofluorescence in PBMCs (Fig. 1C)
Summary
Graves’ disease (GD) is the most common cause of hyperthyroidism, in which patients develop an antithyroid autoimmune response, including lymphocytic infiltration and the presence of autoantibodies against thyroglobulin, thyroid peroxidase and the thyroidstimulating hormone receptor (TSHR) (Weetman 2000). In addition to genetic and environmental factors, immune malfunctions may be involved in the development of GD. It has been suggested that the interaction of antigenpresenting cells, thyroid follicular cells and autoreactive T cells causes an autoimmune response against thyroid antigens (Weetman 2004). The mammalian sirtuin SIRT1 has received much attention for the roles it plays in regulating metabolism and protecting against age-related diseases (Haigis & Sinclair 2010).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
