scholarly journals The Role of Histone Deacetylase and Histone Deacetylase Inhibitors in Rheumatoid Arthritis

2021 ◽  
Vol 5 (11) ◽  
pp. 1211-1218
Author(s):  
Rina Kriswiastiny ◽  
Radiyati Umi Partan ◽  
Hermansyah ◽  
Surya Darma ◽  
Muhammad Reagan
Keyword(s):  
Rheumatoid Arthritis ◽  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitors ◽  
Enzyme Inhibitor ◽  
Systemic Disease ◽  
Cartilage Damage ◽  
Joint Damage ◽  
Synovial Fibroblasts ◽  
Tnf Α

Rheumatoid Arthritis or RA disease is a chronic inflammatory and systemic disease associated with broad synovitis resulting in erosion of the articular cartilage and marginal bone causing joint damage. RA is an autoimmune disease with the discovery of an autoantibody, namely rheumatoid factor. The relevant antibody is anti-citrullinated protein (ACPA) antibody. Citullination on the introduction of several proteins such as fibrin, vimentin, fibronectin, collagen type II, which is expressed in the synovial membrane during inflammation by ACPA. In a recent study increased HDAC activity in the synovial tissue of RA patients has increased. Histone deacetylase or abbreviated as HDAC is an enzyme that is important in regulating gene transcription by altering the acetylation of histone proteins which results in an important regulation of repression in the implementation of inflammation. HDAC enzyme inhibitor (HDACi) is an HDAC enzyme inhibitor that can provide benefits for the treatment of various diseases including malignancy and inflammation. In inflammatory disease HDACi overcomes inflammatory cytokines such as TNF-α, IL-6 and IL-1β. One of the HDAC classes is HDAC1 which is highly expressed in the synovial fibroblasts of RA patients. HDACi can burden swollen joints, reduce mononuclear cell infiltration, request pannus orders, inhibit bone and cartilage damage.

The Role of Synovial Fibroblasts in Mediating Joint Destruction in Rheumatoid Arthritis

2005 ◽  
Vol 11 (5) ◽  
pp. 563-568 ◽  
Author(s):  
Ingmar Meinecke ◽  
Edita Rutkauskaite ◽  
Steffen Gay ◽  
Thomas Pap
Keyword(s):  
Rheumatoid Arthritis ◽  
Joint Destruction ◽  
Synovial Fibroblasts

scholarly journals Prostacyclin-IP signaling and prostaglandin E2-EP2/EP4 signaling both mediate joint inflammation in mouse collagen-induced arthritis

2006 ◽  
Vol 203 (2) ◽  
pp. 325-335 ◽  
Author(s):  
Tetsuya Honda ◽  
Eri Segi-Nishida ◽  
Yoshiki Miyachi ◽  
Shuh Narumiya
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fluid ◽  
Joint Inflammation ◽  
Synovial Fibroblasts ◽  
The Other ◽  
Receptor Subtype ◽  
Significant Suppression ◽  
Wild Type ◽  
Collagen Induced Arthritis

Prostaglandin (PG)I2 (prostacyclin [PGI]) and PGE2 are abundantly present in the synovial fluid of rheumatoid arthritis (RA) patients. Although the role of PGE2 in RA has been well studied, how much PGI2 contributes to RA is little known. To examine this issue, we backcrossed mice lacking the PGI receptor (IP) to the DBA/1J strain and subjected them to collagen-induced arthritis (CIA). IP-deficient (IP−/−) mice exhibited significant reduction in arthritic scores compared with wild-type (WT) mice, despite anti-collagen antibody production and complement activation similar to WT mice. IP−/− mice also showed significant reduction in contents of proinflammatory cytokines, such as interleukin (IL)-6 in arthritic paws. Consistently, the addition of an IP agonist to cultured synovial fibroblasts significantly enhanced IL-6 production and induced expression of other arthritis-related genes. On the other hand, loss or inhibition of each PGE receptor subtype alone did not affect elicitation of inflammation in CIA. However, a partial but significant suppression of CIA was achieved by the combined inhibition of EP2 and EP4. Our results show significant roles of both PGI2-IP and PGE2-EP2/EP4 signaling in the development of CIA, and suggest that inhibition of PGE2 synthesis alone may not be sufficient for suppression of RA symptoms.

scholarly journals Epigenetic Targeting of Autophagy via HDAC Inhibition in Tumor Cells: Role of p53

2018 ◽  
Vol 19 (12) ◽  
pp. 3952 ◽  
Author(s):  
Maria Mrakovcic ◽  
Lauren Bohner ◽  
Marcel Hanisch ◽  
Leopold F. Fröhlich
Keyword(s):  
Cell Death ◽  
Tumor Cells ◽  
Histone Deacetylase ◽  
Stress Responses ◽  
Histone Deacetylase Inhibitors ◽  
Tumor Therapy ◽  
Regulatory System ◽  
Anticancer Activities ◽  
Mutational Status

Tumor development and progression is the consequence of genetic as well as epigenetic alterations of the cell. As part of the epigenetic regulatory system, histone acetyltransferases (HATs) and deacetylases (HDACs) drive the modification of histone as well as non-histone proteins. Derailed acetylation-mediated gene expression in cancer due to a delicate imbalance in HDAC expression can be reversed by histone deacetylase inhibitors (HDACi). Histone deacetylase inhibitors have far-reaching anticancer activities that include the induction of cell cycle arrest, the inhibition of angiogenesis, immunomodulatory responses, the inhibition of stress responses, increased generation of oxidative stress, activation of apoptosis, autophagy eliciting cell death, and even the regulation of non-coding RNA expression in malignant tumor cells. However, it remains an ongoing issue how tumor cells determine to respond to HDACi treatment by preferentially undergoing apoptosis or autophagy. In this review, we summarize HDACi-mediated mechanisms of action, particularly with respect to the induction of cell death. There is a keen interest in assessing suitable molecular factors allowing a prognosis of HDACi-mediated treatment. Addressing the results of our recent study, we highlight the role of p53 as a molecular switch driving HDACi-mediated cellular responses towards one of both types of cell death. These findings underline the importance to determine the mutational status of p53 for an effective outcome in HDACi-mediated tumor therapy.

scholarly journals Role of Histone Deacetylase Inhibitors in Relapsed Refractory Multiple Myeloma: A Focus on Vorinostat and Panobinostat

2015 ◽  
Vol 35 (12) ◽  
pp. 1173-1188 ◽  
Author(s):  
Salma Afifi ◽  
Angela Michael ◽  
Mahshid Azimi ◽  
Mabel Rodriguez ◽  
Nikoletta Lendvai ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitors ◽  
Refractory Multiple Myeloma

scholarly journals Role of Biological Response Modifiers in the Treatment of Rheumatoid Arthritis - A Review

1970 ◽  
Vol 18 (1) ◽  
pp. 60-65
Author(s):  
Md Azizul Haque ◽  
ARM Saifuddin Ekram ◽  
Quazi Tarikul Islam
Keyword(s):  
Rheumatoid Arthritis ◽  
Monoclonal Antibody ◽  
Chronic Disease ◽  
Receptor Antagonist ◽  
Disease Progression ◽  
Joint Damage ◽  
Biological Response ◽  
The Past ◽  
Conventional Dmards

Rheumatoid arthritis is a chronic disease with the potential to cause substantial joint damage and disability. During the past 10 years, improved understanding of the pathophysiology of rheumatoid arthritis has led to several key changes in the approach to therapy. Most important of that is the development of some biological agents interfering with the activity of several important cytokines. Infliximab, etanarcept, and adalimumab are TNF blockers, anakinra is IL-1 receptor antagonist, and rituximab is anti CD-20 monoclonal antibody. These newer agents proved to be useful for alleviating symptoms and slowing the disease progression in the patients with RA who have failed to respond to conventional DMARDs.   doi: 10.3329/taj.v18i1.3309 TAJ 2005; 18(1): 60-65

scholarly journals Peptides Bearing Multiple Post-Translational Modifications as Antigenic Targets for Severe Rheumatoid Arthritis Patients

2021 ◽  
Vol 22 (24) ◽  
pp. 13290
Author(s):  
Cristina García-Moreno ◽  
María J. Gómara ◽  
Raúl Castellanos-Moreira ◽  
Raimon Sanmartí ◽  
Isabel Haro
Keyword(s):  
Rheumatoid Arthritis ◽  
Structural Damage ◽  
Serum Antibody ◽  
Joint Damage ◽  
Erosive Disease ◽  
Post Translational Modifications ◽  
Diagnosis And Prognosis ◽  
Modified Peptides ◽  
Chimeric Peptides

Rheumatoid arthritis (RA) is characterized by the presence of autoantibodies that are of paramount importance for the diagnosis and prognosis of the disease and have been implicated in its pathogenesis. Proteins resulting from post-translational modifications (PTMs) are capable of triggering autoimmune responses important for the development of RA. In this work, we investigate serum antibody reactivity in patients with an established RA against a panel of chimeric peptides derived from fibrin and filaggrin proteins and bearing from one to three PTMs (citrullination, carbamylation and acetylation) by home-designed ELISA tests (anti-AMPA autoantibodies). The role of anti-AMPAs as biomarkers linked to the presence of a more severe RA phenotype (erosive disease with radiological structural damage) and to the presence of interstitial lung disease (ILD), a severe extra-articular manifestation in RA patients entailing a high mortality, was also analyzed. In general, the association with the clinical phenotype of RA was confirmed with the different autoantibodies, and especially for IgA and IgM isotypes. The prevalence of severe joint damage was only statistically significant for the IgG isotype when working with the peptide bearing three PTMs. Furthermore, the median titers were significantly higher in patients with RA-ILD, a finding not observed for the IgG isotype when working with the single- and double-modified peptides.

scholarly journals Multifaceted role of TNF-α during the pathogenesis of rheumatoid arthritis

2013 ◽  
Vol 04 (10) ◽  
pp. 937-940 ◽  
Author(s):  
Ramanjaneya V. R. Mula ◽  
Rangaiah Shashidharamurthy
Keyword(s):  
Rheumatoid Arthritis ◽  
Tnf Α
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