{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T18:26:28Z","timestamp":1792002388370,"version":"4.4.0"},"reference-count":96,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,19]],"date-time":"2022-01-19T00:00:00Z","timestamp":1642550400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Activated rheumatoid arthritis (RA) synovial fibroblasts (SFs) are among the most important cells promoting RA pathogenesis. They are considered active contributors to the initiation, progression, and perpetuation of the disease; therefore, early detection of RASF activation could advance contemporary diagnosis and adequate treatment of undifferentiated early inflammatory arthritis (EA). In this study, we investigated the expression of nucleotide-binding, oligomerization domain (NOD)-like receptor family, pyrin domain containing (NLRP)1, NLRP3 inflammasomes, Toll-like receptor (TLR)1, TLR2, TLR4, vitamin D receptor (VDR), and secretion of matrix metalloproteinases (MMPs) in SFs isolated from patients with RA, osteoarthritis (OA), EA, and control individuals (CN) after knee surgical intervention. C-reactive protein, general blood test, anticyclic citrullinated peptide (anti-CCP), rheumatoid factor (RF), and vitamin D (vitD) in patients\u2019 sera were performed. Cells were stimulated or not with 100 ng\/ml tumor necrosis factor alpha (TNF-\u03b1) or\/and 1 nM or\/and 0.01 nM vitamin D3 for 72 h. The expression levels of <jats:italic>NLRP1<\/jats:italic>, <jats:italic>NLRP3<\/jats:italic>, <jats:italic>TLR1<\/jats:italic>, <jats:italic>TLR2<\/jats:italic>, <jats:italic>TLR4<\/jats:italic>, and <jats:italic>VDR<\/jats:italic> in all examined SFs were analyzed by quantitative real-time PCR (RT-qPCR). Additionally, the secretion of IL-1\u03b2 by SFs and MMPs were determined by ELISA and Luminex technology. The expression of <jats:italic>NLRP3<\/jats:italic> was correlated with the levels of CRP, RF, and anti-CCP, suggesting its implication in SF inflammatory activation. In the TNF-\u03b1-stimulated SFs, a significantly lower expression of <jats:italic>NLRP3<\/jats:italic> and <jats:italic>TLR4<\/jats:italic> was observed in the RA group, compared with the other tested forms of arthritis. Moreover, upregulation of <jats:italic>NLRP3<\/jats:italic> expression by TNF-\u03b1 alone or in combination with vitD3 was observed, further indicating involvement of NLRP3 in the inflammatory responses of SFs. Secretion of IL-1\u03b2 was not detected in any sample, while TNF-\u03b1 upregulated the levels of secreted MMP-1, MMP-7, MMP-8, MMP-12, and MMP-13 in all patient groups. Attenuating effects of vitD on the expression of <jats:italic>NLRP3<\/jats:italic>, <jats:italic>TLR1<\/jats:italic>, and <jats:italic>TLR4<\/jats:italic> suggest potential protective effects of vitD on the inflammatory responses in SFs. However, longer studies may be needed to confirm or fully rule out the potential implication of vitD in SF activation in inflammatory arthritis. Both <jats:italic>VDR<\/jats:italic> and <jats:italic>NLRP3<\/jats:italic> in the TNF-\u03b1-stimulated SFs negatively correlated with the age of patients, suggesting potential age-related changes in the local inflammatory responses.<\/jats:p>","DOI":"10.3389\/fimmu.2021.767512","type":"journal-article","created":{"date-parts":[[2022,1,19]],"date-time":"2022-01-19T05:34:51Z","timestamp":1642570491000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":34,"title":["The Expression of Inflammasomes NLRP1 and NLRP3, Toll-Like Receptors, and Vitamin D Receptor in Synovial Fibroblasts From Patients With Different Types of Knee Arthritis"],"prefix":"10.3389","volume":"12","author":[{"given":"Regina","family":"Sakalyte","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaroslav","family":"Denkovskij","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiva","family":"Bernotiene","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigita","family":"Stropuviene","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvija 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