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Although the exact causes of rheumatic diseases remain unclear, it is evident that ongoing inflammatory reactions are the main factors driving their development. Jumonji domain-containing protein-3 (JMJD3) is an epigenetic modifier that can strongly promote the inflammatory process in many diseases by impacting the Nuclear Factor-\u03baB (NF-\u03baB) signaling. Meanwhile, GSK-J4 has been identified as a selective inhibitor of JMJD3. Therefore, our study aimed at exploring the effects of JMJD3 inhibition by GSK-J4 on inflammasome activation and oxidative stress release in lipopolysaccharide (LPS)-primed patient-derived adherent mononuclear cells of different autoimmune diseases: RA, SLE, and IBD. The inflammatory response was evaluated prior to and following the GSK-J4-cell treatment by assessment of gene and protein expression of inflammatory factors using qRT-PCR and Western blot, respectively. Additionally, cytokine and nitric oxide release in culture supernatants was measured using enzyme-linked immunosorbent assay (ELISA). Our results showed a significant correlation between the inhibition of JMJD3 and the attenuation of inflammatory signaling pathways through reduced NF-\u03baB activation, diminished expression of pro-inflammatory cytokines, and decreased inflammatory stress response. These findings supported the idea that epigenetic modification is a crucial mechanism for priming the inflammasome activation in various autoimmune diseases, confirming the potential of epigenetic factors as prospective therapeutic targets for immune-mediated inflammatory diseases.<\/jats:p>","DOI":"10.1007\/s10787-026-02223-4","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T17:00:38Z","timestamp":1776704438000},"page":"3413-3423","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacological potential of the histone demethylase inhibitor GSK-J4 in mitigating NF-\u03baB-mediated inflammatory cascades associated with autoimmune disorders"],"prefix":"10.1007","volume":"34","author":[{"given":"Ghada Nour","family":"Eldeen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1998-4188","authenticated-orcid":false,"given":"Mona F.","family":"Sokkar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randa S.","family":"Lotfy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hala M.","family":"Raslan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manal","family":"Abd El Moniem El Menyawi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamal A.","family":"El-Atrebi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hala T.","family":"El Bassyouni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,20]]},"reference":[{"key":"2223_CR1","doi-asserted-by":"publisher","first-page":"111250","DOI":"10.1016\/j.intimp.2023.111250","volume":"127","author":"M Adel","year":"2024","unstructured":"Adel M, Hassan R, El-Sayed N, Abdelrahman H, El-Gazzar A (2024) Regulation of inflammatory enzymes iNOS and COX-2 through NF-\u03baB signaling during immune activation. 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