Inhibition of HDAC Activity by ITF2357 Ameliorates Joint Inflammation and Prevents Cartilage and Bone Destruction in Experimental Arthritis

Joosten, Leo A. B.; Leoni, Flavio; Meghji, S; Mascagni, Paolo

doi:10.2119/molmed.2011.00058

Cited by 91 publications

(57 citation statements)

References 40 publications

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“…These dose-dependent effects of panobinostat closely resemble the effects of butyrate, suggesting that a similar mechanism is involved. Addition of givinostat, which is a well-known pan-HDAC inhibitor that was reported to have beneficial effects in several forms of arthritis in vivo,15 16 decreased LPS-induced IL-1β at 25 nM. This is consistent with a previous study in human PBMCs 24.…”

Section: Discussionsupporting

confidence: 90%

“…Recently, the synthetic pan-HDAC inhibitor givinostat was shown to have a broad anti-inflammatory activity with beneficial effects in experimental models of arthritis and even led to attenuation of clinical scores in a trial with patients with juvenile idiopathic arthritis 15 16. Inhibition of HDACs might therefore also have beneficial effects in acute gouty arthritis.…”

Section: Introductionmentioning

confidence: 99%

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Suppression of monosodium urate crystal-induced cytokine production by butyrate is mediated by the inhibition of class I histone deacetylases

et al. 2015

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In agreement with the reported low inhibitory potency of butyrate, a high concentration was needed for cytokine suppression, whereas synthetic HDAC inhibitors showed potent anti-inflammatory effects at nanomolar concentrations. These novel HDAC inhibitors could be effective in the treatment of acute gout. Moreover, the use of specific HDAC inhibitors could even improve the efficacy and reduce any potential adverse effects.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Suppression of monosodium urate crystal-induced cytokine production by butyrate is mediated by the inhibition of class I histone deacetylases

et al. 2015

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“…HDAC inhibitors are the best studied epigenetic therapeutic agents and have been proven to reduce the levels of proinflammatory cytokines (Leoni et al 2005) (Leoni et al 2002). Beneficial effects of HDAC inhibitors have been initially described in animal models of arthritis (Nishida et al 2004) (Lin et al 2007) (Nasu et al 2008) (Saouaf et al 2009) (Joosten et al 2011). In humans 18 HDACs have been described and further characterized (Wang et al 2009b).…”

Section: Gene Expression Genomes and Chromatin Organizationmentioning

confidence: 99%

Helper T Cell Plasticity: Impact of Extrinsic and Intrinsic Signals on Transcriptomes and Epigenomes

Bonelli

Shih

Hirahara

et al. 2014

Current Topics in Microbiology and Immunology

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CD4+ helper T cells are crucial for autoimmune and infectious diseases; however, the recognition of the many, diverse fates available continues unabated. Precisely what controls specification of helper T cells and preserves phenotypic commitment is currently intensively investigated. In this review, we will discuss the major factors that impact helper T cell fate choice, ranging from cytokines and the microbiome to metabolic control and epigenetic regulation. We will also discuss the technological advances along with the attendant challenges presented by “big data”, which allow the understanding of these processes on comprehensive scales.

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“…It results in reduced cartilage destruction, bone breakdown, joint swelling and pro-inflammatory cytokine expression by synovial cells and tissue. Furthermore, it reduced the total number of cells arriving at the inflamed joint [60]. More recently, a clinical trial of this agent in systemiconset idiopathic juvenile arthritis resulted in reduced numbers of leucocytes, fewer active arthritic joints and reduced expression of inflammatory cytokines, while remaining safe and beneficial for the patient [61].…”

Section: Histone Acetylation In Ra Murine Models and Human Arthritic mentioning

confidence: 99%

The role of histone deacetylases in rheumatoid arthritis fibroblast-like synoviocytes

Hawtree

Muthana

Wilson

2013

Biochemical Society Transactions

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RA (rheumatoid arthritis) is an inflammatory disease of synovial joints affecting approximately 1% of the population. One of the main cell types involved in damage to RA joint tissue is the FLSs (fibroblast-like synoviocytes). These have a semi-transformed, auto-aggressive phenotype typified by loss of contact inhibition, reduced apoptosis and the production of matrix-degrading enzymes. The mechanisms involved in the development of this phenotype are unclear; however, increasing evidence implicates alterations in the epigenetic regulation of gene expression. Reduced acetylation of amino acids in the tails of histone proteins is an epigenetic mark associated with transcriptional repression and is controlled by the HDAC (histone deacetylase) enzyme family. To date, evidence has implicated HDACs in the auto-aggressive phenotype of FLSs, and administration of HDAC inhibitors to both animal models of RA and individuals with juvenile arthritis has shown efficacy in attenuating inflammation and tissue damage. This highlights a role for HDACs in disease pathogenesis and, more importantly, that HDACs are potential novel therapeutic targets.

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Inhibition of HDAC Activity by ITF2357 Ameliorates Joint Inflammation and Prevents Cartilage and Bone Destruction in Experimental Arthritis

Cited by 91 publications

References 40 publications

Suppression of monosodium urate crystal-induced cytokine production by butyrate is mediated by the inhibition of class I histone deacetylases

Suppression of monosodium urate crystal-induced cytokine production by butyrate is mediated by the inhibition of class I histone deacetylases

Helper T Cell Plasticity: Impact of Extrinsic and Intrinsic Signals on Transcriptomes and Epigenomes

The role of histone deacetylases in rheumatoid arthritis fibroblast-like synoviocytes

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