Activation of Liver X Receptors Suppresses Inflammatory Gene Expressions and Transcriptional Corepressor Clearance in Rheumatoid Arthritis Fibroblast Like Synoviocytes

2012 ◽  
Vol 33 (1) ◽  
pp. 190-199 ◽  
Author(s):  
Chong-Hyeon Yoon ◽  
Yong-Jin Kwon ◽  
Sang-Won Lee ◽  
Yong-Beom Park ◽  
Soo-Kon Lee ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Liver X Receptors ◽  
Transcriptional Corepressor ◽  
Gene Expressions ◽  
Inflammatory Gene ◽  
X Receptors ◽  
Fibroblast Like Synoviocytes

AB0112 Caspase-5 inhibitor suppresses pro-inflammatory gene expressions in fibroblast like synoviocytes from patients with rheumatoid arthritis

2013 ◽  
Vol 72 (Suppl 3) ◽  
pp. A819.3-A819
Author(s):  
Y.-J. Kwon ◽  
T.-Y. Kim ◽  
S.-W. Lee ◽  
Y.-B. Park ◽  
S.-K. Lee ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expressions ◽  
Inflammatory Gene ◽  
Fibroblast Like Synoviocytes

scholarly journals The liver X receptor pathway is highly upregulated in rheumatoid arthritis synovial macrophages and potentiates TLR-driven cytokine release

2013 ◽  
Vol 72 (12) ◽  
pp. 2024-2031 ◽  
Author(s):  
Darren Lee Asquith ◽  
Lucy E Ballantine ◽  
Jagtar Singh Nijjar ◽  
Manhal Khuder Makdasy ◽  
Sabina Patel ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cholesterol Metabolism ◽  
Liver X Receptors ◽  
Blood Monocytes ◽  
Functional Studies ◽  
Inflammatory Processes ◽  
X Receptors ◽  
Factor Α ◽  
Necrosis Factor ◽  
Tlr Signalling

ObjectivesMacrophages are central to the inflammatory processes driving rheumatoid arthritis (RA) synovitis. The molecular pathways that are induced in synovial macrophages and thereby promote RA disease pathology remain poorly understood.MethodsWe used microarray to characterise the transcriptome of synovial fluid (SF) macrophages compared with matched peripheral blood monocytes from patients with RA (n=8).ResultsUsing in silico pathway mapping, we found that pathways downstream of the cholesterol activated liver X receptors (LXRs) and those associated with Toll-like receptor (TLR) signalling were upregulated in SF macrophages. Macrophage differentiation and tumour necrosis factor α promoted the expression of LXRα. Furthermore, in functional studies we demonstrated that activation of LXRs significantly augmented TLR-driven cytokine and chemokine secretion.ConclusionsThe LXR pathway is the most upregulated pathway in RA synovial macrophages and activation of LXRs by ligands present within SF augments TLR-driven cytokine secretion. Since the natural agonists of LXRs arise from cholesterol metabolism, this provides a novel mechanism that can promote RA synovitis.

Liver X receptors conserve the therapeutic target potential for the treatment of Rheumatoid arthritis

2021 ◽  
pp. 105747
Author(s):  
Chu-Tian Mai ◽  
De-Chong Zheng ◽  
Xin-zhi Li ◽  
Hua Zhou ◽  
Ying Xie
Keyword(s):  
Rheumatoid Arthritis ◽  
Therapeutic Target ◽  
Liver X Receptors ◽  
X Receptors

scholarly journals Histone deacetylase 3 regulates the inflammatory gene expression programme of rheumatoid arthritis fibroblast-like synoviocytes

2016 ◽  
Vol 76 (1) ◽  
pp. 277-285 ◽  
Author(s):  
Chiara Angiolilli ◽  
Pawel A Kabala ◽  
Aleksander M Grabiec ◽  
Iris M Van Baarsen ◽  
Bradley S Ferguson ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
Dna Binding ◽  
Histone Deacetylase ◽  
Type I ◽  
Type I Ifn ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene ◽  
Inducible Genes ◽  
Fibroblast Like Synoviocytes

ObjectivesNon-selective histone deacetylase (HDAC) inhibitors (HDACi) have demonstrated anti-inflammatory properties in both in vitro and in vivo models of rheumatoid arthritis (RA). Here, we investigated the potential contribution of specific class I and class IIb HDACs to inflammatory gene expression in RA fibroblast-like synoviocytes (FLS).MethodsRA FLS were incubated with pan-HDACi (ITF2357, givinostat) or selective HDAC1/2i, HDAC3/6i, HDAC6i and HDAC8i. Alternatively, FLS were transfected with HDAC3, HDAC6 or interferon (IFN)-α/β receptor alpha chain (IFNAR1) siRNA. mRNA expression of interleukin (IL)-1β-inducible genes was measured by quantitative PCR (qPCR) array and signalling pathway activation by immunoblotting and DNA-binding assays.ResultsHDAC3/6i, but not HDAC1/2i and HDAC8i, significantly suppressed the majority of IL-1β-inducible genes targeted by pan-HDACi in RA FLS. Silencing of HDAC3 expression reproduced the effects of HDAC3/6i on gene regulation, contrary to HDAC6-specific inhibition and HDAC6 silencing. Screening of the candidate signal transducers and activators of transcription (STAT)1 transcription factor revealed that HDAC3/6i abrogated STAT1 Tyr701 phosphorylation and DNA binding, but did not affect STAT1 acetylation. HDAC3 activity was required for type I IFN production and subsequent STAT1 activation in FLS. Suppression of type I IFN release by HDAC3/6i resulted in reduced expression of a subset of IFN-dependent genes, including the chemokines CXCL9 and CXCL11.ConclusionsInhibition of HDAC3 in RA FLS largely recapitulates the effects of pan-HDACi in suppressing inflammatory gene expression, including type I IFN production in RA FLS. Our results identify HDAC3 as a potential therapeutic target in the treatment of RA and type I IFN-driven autoimmune diseases.

Gallic acid, a natural polyphenolic acid, induces apoptosis and inhibits proinflammatory gene expressions in rheumatoid arthritis fibroblast-like synoviocytes

2013 ◽  
Vol 80 (3) ◽  
pp. 274-279 ◽  
Author(s):  
Chong-Hyeon Yoon ◽  
Soo-Jin Chung ◽  
Sang-Won Lee ◽  
Yong-Beom Park ◽  
Soo-Kon Lee ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gallic Acid ◽  
Gene Expressions ◽  
Proinflammatory Gene ◽  
Fibroblast Like Synoviocytes

Using integrative lipid systems biology to understand the role of Liver X receptors (LXRs) in male reproduction

2018 ◽  
Author(s):  
Sheba Jarvis ◽  
Lee Gethings ◽  
Raffaella Gadeleta ◽  
Emmanuelle Claude ◽  
Robert Winston ◽  
...  
Keyword(s):  
Systems Biology ◽  
Male Reproduction ◽  
Liver X Receptors ◽  
X Receptors

Treatment with Melittin Induces Apoptosis and Autophagy of Fibroblast-like Synoviocytes in Patients with Rheumatoid Arthritis

2020 ◽  
Vol 21 (8) ◽  
pp. 734-740 ◽  
Author(s):  
Shou-di He ◽  
Ning Tan ◽  
Chen-xia Sun ◽  
Kang-han Liao ◽  
Hui-jun Zhu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Caspase 3 ◽  
Joint Destruction ◽  
Joint Disease ◽  
Enzyme Linked Immunosorbent Assay ◽  
Caspase 9 ◽  
Inflammatory Processes ◽  
Related Proteins ◽  
Local Stimulation ◽  
Fibroblast Like Synoviocytes

Background: Melittin, the major medicinal component of honeybee venom, exerts antiinflammatory, analgesic, and anti-arthritic effects in patients with Rheumatoid Arthritis (RA). RA is an inflammatory autoimmune joint disease that leads to irreversible joint destruction and functional loss. Fibroblast-Like Synoviocytes (FLS) are dominant, special mesenchymal cells characterized by the structure of the synovial intima, playing a crucial role in both the initiation and progression of RA. Objective: In this study, we evaluated the effects of melittin on the viability and apoptosis of FLS isolated from patients with RA. Methods: Cell viability was determined using CCK-8 assays; apoptosis was evaluated by flow cytometry, and the expression levels of apoptosis-related proteins (caspase-3, caspase-9, BAX, and Bcl-2) were also determined. To explore whether melittin alters inflammatory processes in RA-FLS, IL-1β levels were determined using an enzyme-linked immunosorbent assay (ELISA). Furthermore, we performed GFP-LC3 punctate fluorescence dot assays and western blotting (for LC3, ATG5, p62, and Beclin 1) to assess autophagy in RA-FLS. Results: Our results show that melittin can significantly impair viability, promote apoptosis and autophagy, and inhibit IL-1β secretion in RA-FLS. Conclusion: Melittin may be useful in preventing damage to the joints during accidental local stimulation.

Sign in / Sign up

Export Citation Format

Share Document