Activation of RXR by bexarotene inhibits inflammatory conditions in human rheumatoid arthritis fibroblast‑like synoviocytes.

08:00 EDT 10th September 2019 | BioPortfolio

Summary of "Activation of RXR by bexarotene inhibits inflammatory conditions in human rheumatoid arthritis fibroblast‑like synoviocytes."

Rheumatoid arthritis (RA) is a debilitating joint disease characterized by chronic inflammation, pathologic alteration of fibroblast‑like synoviocytes (FLS), destruction of cartilage and bone, and the formation of an invasive pannus. RA‑FLS exhibit increased proliferation and resistance to apoptosis. The retinoid X receptor (RXR) has a role in regulating cell cycle, differentiation and apoptosis, and agonism of RXR has been investigated as a treatment strategy in several types of cancer. However, there is little research on the effects of RXR agonism in other diseases. Bexarotene is a novel selective RXR ligand used in the treatment of T‑cell lymphoma. In the present study, bexarotene was used to investigate the involvement of RXR in tumor necrosis factor‑α (TNF‑α)‑induced RA conditions in human FLS. To the best of our knowledge, this is the first time that RXR has been demonstrated to be expressed in FLS and to be downregulated in response to TNF‑α stimulation. The present study also demonstrated that bexarotene exerted an anti‑inflammatory effect by downregulating expression of interleukin (IL)‑6, IL‑8, monocyte chemoattractant protein‑1, and high mobility group box‑1. Notably, bexarotene also rescued the TNF‑α‑induced downregulation of the anti‑inflammatory cytokines IL‑4 and transforming growth factor‑β1. Bexarotene treatment exhibited a potential protective effect against cartilage degradation by downregulating the expression of matrix metalloproteinase (MMP)‑1, MMP‑3 and MMP‑13. In addition, the present results demonstrated that the effects of bexarotene were mediated through the p38 mitogen‑activated protein kinase/nuclear factor‑κB pathway, via inhibition of p38 protein and the inhibitor α of κB phosphorylation. Taken together, the present findings demonstrated the potential of RXR agonism using bexarotene as a treatment against the development and progression of RA.


Journal Details

This article was published in the following journal.

Name: International journal of molecular medicine
ISSN: 1791-244X


DeepDyve research library

PubMed Articles [26809 Associated PubMed Articles listed on BioPortfolio]

Perceived stress and inflammatory arthritis: a prospective investigation in the Studies of the Etiologies of Rheumatoid Arthritis (SERA) cohort.

The aim of this study was to determine the association of perceived stress with incident inflammatory arthritis (IA) defined as having at least 1 joint consistent with rheumatoid arthritis (RA)-like s...

ATP and adenosine: role in the immunopathogenesis of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a classic inflammatory autoimmune disease. Local joint destruction and extra-articular manifestations of RA deeply compromise the life quality of the affected patients. RA...

Meroterpenoid-Rich Fraction of the Ethanol Extract of Sargassum Serratifolium Suppresses Collagen-Induced Rheumatoid Arthritis in DBA/1J Mice Via Inhibition of Nuclear Factor κB Activation.

Rheumatoid arthritis (RA) is an autoimmune disorder related to the inflammation of cartilage due to the infiltration of inflammatory cells. Sargassum serratifolium, a brown alga, possesses strong anti...

CYP-derived eicosanoids: Implications for rheumatoid arthritis.

Today the role of cytochrome P450 metabolites in inflammatory rheumatic disease, such as rheumatoid arthritis (RA) is still poorly understood. In this review we survey the current knowledge on cytochr...

Chondrocytes play a role in the development of rheumatoid arthritis via TMEM147-mediated NF-κB activation.

We previously reported that the co-activation of NF-κB and STAT3 in non-immune cells including synovial fibroblasts enhances the expression of NF-κB target genes, playing a role in chronic inflammat...

Clinical Trials [12400 Associated Clinical Trials listed on BioPortfolio]

Faecal Calprotectin as a Potential Non-invasive Inflammatory Marker in Pregnancy and Inflammatory Bowel Disease

When women with rheumatoid arthritis become pregnant 75% of them will go into remission, despite stopping medication. This phenomenon is not well understood and is not seen in other inflam...

Methotrexate and Metformin in Rheumatoid Arthritis Patients

Methotrexate (MTX) is the anchor drug for patients with rheumatoid arthritis (RA). Despite its marked efficacy and acceptable side effect profile, about 1/3 of patients failed to reach RA ...

Efficacy and Safety of TwHF and MTX in Patients With Rheumatoid Arthritis

Rheumatoid Arthritis (RA) is an autoimmune disease that results in a chronic inflammatory disorder that may affect many synovial joints, and may cause serious disability. It has been confi...

ADIRA (Anti-inflammatory Diet In Rheumatoid Arthritis): a Randomized Cross-over Trial

Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects 0.5-1% of the population, and where many patients in spite of modern pharmacological treatment fail to reach remiss...

Relationship of Periodontitis and Cardiovascular Risk in Patients With Rheumatoid Arthritis

Rheumatoid arthritis (RA) is one of the most common autoimmune inflammatory arthritis affecting 0.5 to 1% population worldwide characterized by synovitis, increased inflammatory markers an...

Medical and Biotech [MESH] Definitions

A recombinant version of soluble human TNF receptor that binds specifically to TUMOR NECROSIS FACTOR and inhibits its binding with endogenous TNF receptors. It prevents the inflammatory effect of TNF and is used to treat RHEUMATOID ARTHRITIS; PSORIATIC ARTHRITIS and ANKYLOSING SPONDYLITIS.

A fusion protein immunoconjugate of the extracellular domain of CTLA4 and the Fc domain of human IgG1. It functions as a T-cell co-stimulation blocker that inhibits TNF-ALPHA and prevents the activation of T-LYMPHOCYTES. It is used in the treatment of RHEUMATOID ARTHRITIS.

Arthritis in children, with onset before 16 years of age. The terms juvenile rheumatoid arthritis (JRA) and juvenile idiopathic arthritis (JIA) refer to classification systems for chronic arthritis in children. Only one subtype of juvenile arthritis (polyarticular-onset, rheumatoid factor-positive) clinically resembles adult rheumatoid arthritis and is considered its childhood equivalent.

A variable mixture of the mono- and disodium salts of gold thiomalic acid used mainly for its anti-inflammatory action in the treatment of rheumatoid arthritis. It is most effective in active progressive rheumatoid arthritis and of little or no value in the presence of extensive deformities or in the treatment of other forms of arthritis.

Rheumatoid arthritis of children occurring in three major subtypes defined by the symptoms present during the first six months following onset: systemic-onset (Still's Disease, Juvenile-Onset), polyarticular-onset, and pauciarticular-onset. Adult-onset cases of Still's disease (STILL'S DISEASE, ADULT-ONSET) are also known. Only one subtype of juvenile rheumatoid arthritis (polyarticular-onset, rheumatoid factor-positive) clinically resembles adult rheumatoid arthritis and is considered its childhood equivalent.

Quick Search

DeepDyve research library

Relevant Topics

Arthroplasty Joint Disorders Orthopedics Spinal Cord Disorders Orthopedics is the science or practice of correcting deformities caused by disease or damage to the bones and joints of the skeleton. This specialized branch of surgery may ...

Arthritis Fibromyalgia Gout Lupus Rheumatic Rheumatology is the medical specialty concerned with the diagnosis and management of disease involving joints, tendons, muscles, ligaments and associated structures (Oxford Medical Diction...

Searches Linking to this Article