Reduced Activity of HDAC3 and Increased Acetylation of Histones H3 in Peripheral Blood Mononuclear Cells of Patients with Rheumatoid Arthritis.

Yan Li,Xiaoqing Yuan,Mi Zhou,Dashan Wang,Di Zhang,Lina Song,Guixiu Shi,Xiuying Lv,Xue Zhao,Mian Wang,Yan He

doi:10.1155/2018/7313515

Abstract

Aberrant histone acetylation and deacetylation are increasingly thought to play important roles in the pathogenesis of rheumatoid arthritis (RA). However, limited data from studies about the activity of histone deacetylases (HDACs) and histone acetyltransferase (HAT) in RA are controversial. Those conflicting results may be caused by sample size, medication, and age- and sex-matched controls. The aim of this study is to investigate the expression and activity of class I HDACs (1–3.8) and their effects on histone acetylation in peripheral blood mononuclear cells (PBMCs) from RA patients. The expression of class I HDACs in PBMCs from RA patients was decreased in both mRNA and protein levels in comparison with HCs. The nuclear HAT activities were dramatically increased. Further, we found HDAC3 activity to be the most significantly reduced in overall reduction of HDACs in the RA group. The extent of total histone H3, but not H4, acetylation in PBMCs from RA patients was increased compared to that in healthy controls (HCs) (p < 0.01). In RA PBMCs, the activity and expression of class I HDACs are decreased, which is accompanied with enhanced HAT activity. An altered balance between HDAC and HAT activity was found in RA PBMCs.

Highlights

Rheumatoid arthritis (RA) is a chronic autoimmune disease mostly of unknown etiology, and a key characteristic of the disease is progressive destruction of articular cartilage [1]
To assess the activity of histone deacetylases (HDACs) in peripheral blood mononuclear cells (PBMCs) from patients with RA, we measured the mRNA expression of HDACs in PBMCs from RA patients and healthy controls (HCs) by real-time PCR
The protein expression levels of total HDAC1, HDAC2, HDAC3, and HDAC8 were lower in RA PBMCs when compared with HC PBMCs (Figures 1(b) and 1(c))

Summary

Introduction

Rheumatoid arthritis (RA) is a chronic autoimmune disease mostly of unknown etiology, and a key characteristic of the disease is progressive destruction of articular cartilage [1]. Especially PBMCs secreting abnormal levels of pro- and anti-inflammatory cytokines infecting T helper (Th) cells differentiating towards Th1, Th2, Th17, and Treg cells, was involved in the evolution of the disease [2]. Accumulating evidence suggests that epigenetic changes, including histone modifications, play an important role in proinflammatory cytokine secretion in RA [3,4,5]. There are at least eighteen HDACs in mammal cells that are categorized into four classes: class I (HDAC 1, 2, 3, and 8), class II (HDAC 4, 5, 6, 7, 9, and 10), class III (SIRT 1–7), and class IV (HDAC 11) [8]. Class I HDACs are ubiquitously expressed and enzymatically active to deacetylase histones and play an important role in modulating general cellular processes such as cell survival, apoptosis, proliferation, Journal of Immunology Research and differentiation [8, 9]. In this study, we focus on class I HDACs

Objectives

Methods

Results

Conclusion