Cystathionine-γ-lyase ameliorates the histone demethylase JMJD3-mediated autoimmune response in rheumatoid arthritis

Cellular & Molecular Immunology
Weijun WuYi Zhun Zhu

Abstract

Cystathionine-γ-lyase (CSE), an enzyme associated with hydrogen sulfide (H2S) production, is an important endogenous regulator of inflammation. Jumonji domain-containing protein 3 (JMJD3) is implicated in the immune response and inflammation. Here, we investigated the potential contribution of JMJD3 to endogenous CSE-mediated inflammation in rheumatoid arthritis (RA). Upregulated CSE and JMJD3 were identified in synovial fibroblasts (SFs) from RA patients as well as in the joints of arthritic mice. Knocking down CSE augmented inflammation in IL-1β-induced SFs by increasing JMJD3 expression. In addition, CSE-/- mice with collagen-induced arthritis (CIA) developed severe joint inflammation and bone erosion. Conversely, overexpressing CSE inhibited JMJD3 expression by the transcription factor Sp-1 and was accompanied by reduced inflammation in IL-1β-treated SFs. Furthermore, JMJD3 silencing or the administration of the JMJD3 inhibitor GSK-J4 significantly decreased the inflammatory response in IL-1β-treated SFs, mainly by controlling the methylation status of H3K27me3 at the promoter of its target genes. GSK-J4 markedly attenuated the severity of arthritis in CIA mice. In conclusion, suppressing JMJD3 expression by the transcripti...Continue Reading

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Citations

Jan 23, 2021·Free Radical Biology & Medicine·Hannah Petraitis KuschmanDouglas D Thomas
Oct 27, 2020·Frontiers in Pharmacology·Qian DingYi Zhun Zhu
Aug 12, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Nahzli DilekCsaba Szabo
Jul 30, 2021·Cellular & Molecular Immunology·Ran WangYi Zhun Zhu

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Methods Mentioned

BETA
transfection
enzyme-linked immunosorbent assay
PCR
ELISA
ChIP
ChIP-PCR

Software Mentioned

GraphPad Prism
ALGGEN
R

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