HDAC Inhibition in Rheumatoid Arthritis and Juvenile Idiopathic Arthritis

Vojinović, Jelena; Damjanov, Nemanja

doi:10.2119/molmed.2011.00030

Cited by 104 publications

(71 citation statements)

References 58 publications

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“…The effects of trichostatin A on human T cells are predominantly immunosuppressive and reminiscent of the signaling aberrations described in patients with SLE. HDAC inhibition is also effective in the treatment of juvenile idiopathic arthritis [33]. Additionally, potential therapeutic roles for DNA demethylation inhibitors are currently being investigated, and MBD2 was recently proposed as a candidate target [34].…”

Section: Discussionmentioning

confidence: 99%

Abnormal Epigenetic Modifications in Peripheral T Cells from Patients with Abdominal Aortic Aneurysm Are Correlated with Disease Development

Jiang

Xin²,

Xin³

et al. 2015

J Vasc Res

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Background: Increasing evidence suggests that abdominal aortic aneurysm (AAA) is a T-cell-mediated autoimmune condition. This study investigates the epigenetic modifications that occur in the T cells of AAA patients and evaluates the correlation of these modifications with disease development. Methods and Results: Peripheral T cells were collected from 101 AAA patients and 102 healthy controls (HCs). DNA methylation and histone acetylation levels were measured by ELISA. Methyl-CpG-binding domain, DNA methyltransferase (DNMT) and histone deacetylase (HDAC) mRNA levels were determined by real-time PCR. DNA from the T cells of the AAA patients exhibited significant hypomethylation compared with the HCs (1.6-fold, p < 0.0001). Expression of DNMT1 at the mRNA level in the T cells of the AAA patients was 1.52-fold lower than that of the HCs (p < 0.0001). The extent of DNA methylation in the AAA patients was negatively correlated with the corresponding aortic diameter (r = -0.498, p < 0.0001). H3 (1.59-fold, p < 0.0001) and H3K14 (2.15-fold, p < 0.0001) acetylation levels in the T cells of the AAA patients were higher than those of the HCs, but the HDAC1 mRNA level was 2.33-fold lower than that of the HCs (p < 0.0001). Conclusions: DNA methylation and the histone modification status are significantly altered in the T cells of AAA patients. These changes could play a pivotal role in the activation of pathological immune responses and may influence AAA development.

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Section: Discussionmentioning

confidence: 99%

Abnormal Epigenetic Modifications in Peripheral T Cells from Patients with Abdominal Aortic Aneurysm Are Correlated with Disease Development

Jiang

Xin²,

Xin³

et al. 2015

J Vasc Res

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“…[172][173][174] Interestingly, a polymorphism in TLE1, a HDAC-interacting transcription factor, is associated with CD. 175 On the other hand, HDAC inhibitors improve experimental colitis and kidney disease in mice 176,177 and are undergoing evaluation as therapy for inflammatory diseases, such as systemic onset juvenile idiopathic arthritis 178 and IBD. 179 The therapeutic properties of HDAC inhibitors are incompletely understood and may involve mechanisms independent of inflammatory gene regulation, including protein acetylation and the induction of apoptosis.…”

Section: Epigenetic Regulation Of Prr Signalingmentioning

confidence: 99%

Negative regulation of human mononuclear phagocyte function

Hedl

Abraham

2013

Mucosal Immunology

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At mucosal surfaces, phagocytes such as macrophages coexist with microbial communities; highly controlled regulation of these interactions is essential for immune homeostasis. Pattern-recognition receptors (PRRs) are critical in recognizing and responding to microbial products, and they are subject to negative regulation through various mechanisms, including downregulation of PRR-activating components or induction of inhibitors. Insights into these regulatory mechanisms have been gained through human genetic disease-association studies, in vivo mouse studies utilizing disease models or targeted gene perturbations, and in vitro and ex vivo human cellular studies examining phagocytic cell functions. Although mouse models provide an important approach to study macrophage regulation, human and mouse macrophages exhibit differences, which must be considered when extrapolating mouse findings to human physiology. This review discusses inhibitory regulation of PRR-induced macrophage functions and the consequences of dysregulation of these functions and highlights mechanisms that have a role in intestinal macrophages and in human macrophage studies.

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“…It is clinically well tolerated and has been used in the treatment of systemic-onset juvenile idiopathic arthritis in children [26]. Recently, it has emerged as a promising oral KDACi drug to target islet inflammation in both T1DM and T2DM.…”

Section: Givinostatmentioning

confidence: 99%