Overexpression of sirtuin 6 suppresses allergic airway inflammation through deacetylation of GATA3

Abstract

levels by 27.4%. In an in vitro study, dexamethasone did not suppress TGF-b-induced production of periostin by fibroblasts, 8 although it did suppress IL-4/IL-13-induced production of periostin. Therefore, TGF-b-induced periostin would play a role in the development of corticosteroid insensitivity, and interaction between eosinophils and periostin may be involved in this process. The limitation of this study is that we only conducted an in vitro study. Whether interaction between eosinophils and periostin actually occurs in blood or airways in patients with asthma is still unknown because the concentration of periostin that we coated on the plates was much higher than that in serum and bronchoalveolar lavage fluid. 3,10 However, we postulate that periostin could directly activate eosinophils in some situations, probably in patients with T H 2-high asthma or with airway remodeling. Here, we report that periostin upregulates eosinophil functions such as O 2 2 generation and EDN release through aMb2 integrin. Furthermore, periostin increases the production of TGF-b and cysLTs from eosinophils. These effects may be involved in the activation of eosinophils in the airway of T H 2-dominant asthma, and promote airway remodeling. We thank Ms Akemi Yokote for her excellent technical assistance.

Myeloid sirtuin 6 deficiency accelerates experimental rheumatoid arthritis by enhancing macrophage activation and infiltration into synovium

“…Accordingly, overexpression of Sirt6 downregulates local and systemic levels of proinflammatory cytokines and attenuates bone destruction in mice with collagen-induced arthritis [10,11]. As a non-histone protein deacetylase, Sirt6 deacetylates GCN5 [12], pyruvate kinase M2 [13], forkhead box protein O1 (FoxO1) [14], and GATA binding protein 3 [15]. Based on the prominent role of Sirt6 in inflammatory and migration responses of macrophages, we investigated the functional responses of wild type (WT) and myeloid Sirt6 knockout (mS6KO) mice in collagen-induced arthritis (CIA) and K/BxN serum transfer arthritis models, which are known to be highly dependent on chronic adaptive immunity and acute passive immunity, respectively.…”

Myeloid Sirtuin 6 Deficiency Causes Insulin Resistance in High-Fat Diet–Fed Mice by Eliciting Macrophage Polarization Toward an M1 Phenotype

“…In contrast, ablation of neural Sirt6 causes obesity (12). Additional evidence for the anti-inflammatory properties of Sirt6 has been provided in autoimmune disease and allergic airway inflammation models (13,14).…”

Hepatocyte‐specific sirtuin 6 deletion predisposes to nonalcoholic steatohepatitis by up‐regulation of Bach1, an Nrf2 repressor

“…Accordingly, overexpression of Sirt6 suppressed collagen‐induced arthritis in mice (15) and cytokine production in vitro (16), whereas the lack of Sirt6 caused the chronic liver inflammation (17) and impaired wound healing (18). In addition to histone H3, Sirt6 directly deacetylates the C‐terminal binding protein interacting protein (19), acetyltransferase GCN5 (20), forkhead box protein O1 (21), and GATA binding protein 3 (22).…”