{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:18:00Z","timestamp":1779927480351,"version":"3.53.1"},"reference-count":53,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2019,12,18]],"date-time":"2019-12-18T00:00:00Z","timestamp":1576627200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Interleukin (IL)-18 expression in synovial tissue correlates with the severity of joint inflammation and the levels of pro-inflammatory cytokines. However, the role of the IL-18\/IL-18 receptor-alpha (R\u03b1) signaling pathway in autoimmune arthritis is unknown. Wild-type (WT) and IL-18R\u03b1 knockout (KO) mice were immunized with bovine type II collagen before the onset of arthritis induced by lipopolysaccharide injection. Disease activity was evaluated by semiquantitative scoring and histologic assessment. Serum inflammatory cytokine and anticollagen antibody levels were quantified by an enzyme-linked immunosorbent assay. Joint cytokine and matrix metalloproteinases-3 levels were determined by a quantitative polymerase chain reaction. Splenic suppressors of cytokine signaling (SOCS) were determined by Western blot analysis as indices of systemic immunoresponse. IL-18R\u03b1 KO mice showed lower arthritis and histological scores in bone erosion and synovitis due to reductions in the infiltration of CD4+ T cells and F4\/80+ cells and decreased serum IL-6, -18, TNF, and IFN-\u03b3 levels. The mRNA expression and protein levels of SOCS3 were significantly increased in the IL-18R\u03b1 KO mice. By an up-regulation of SOCS, pro-inflammatory cytokines were decreased through the IL-18\/IL-18R\u03b1 signaling pathway. These results suggest that inhibitors of the IL-18\/IL-18R\u03b1 signaling pathway could become new therapeutic agents for rheumatoid arthritis.<\/jats:p>","DOI":"10.3390\/cells9010011","type":"journal-article","created":{"date-parts":[[2019,12,23]],"date-time":"2019-12-23T03:23:12Z","timestamp":1577071392000},"page":"11","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Inhibition of the IL-18 Receptor Signaling Pathway Ameliorates Disease in a Murine Model of Rheumatoid Arthritis"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2810-1519","authenticated-orcid":false,"given":"Yuji","family":"Nozaki","sequence":"first","affiliation":[{"name":"Department of Hematology and Rheumatology, Kindai University Faculty of Medicine; Osaka-sayama, Osaka 589-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhai","family":"Ri","sequence":"additional","affiliation":[{"name":"Department of Hematology and Rheumatology, Kindai University Faculty of Medicine; Osaka-sayama, Osaka 589-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Sakai","sequence":"additional","affiliation":[{"name":"Department of Hematology and Rheumatology, Kindai University Faculty of Medicine; Osaka-sayama, Osaka 589-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaoru","family":"Niki","sequence":"additional","affiliation":[{"name":"Department of Hematology and Rheumatology, Kindai University Faculty of Medicine; Osaka-sayama, Osaka 589-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Kinoshita","sequence":"additional","affiliation":[{"name":"Department of Hematology and Rheumatology, Kindai University Faculty of Medicine; Osaka-sayama, Osaka 589-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanori","family":"Funauchi","sequence":"additional","affiliation":[{"name":"Department of Hematology and Rheumatology, Kindai University Faculty of Medicine; Osaka-sayama, Osaka 589-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Itaru","family":"Matsumura","sequence":"additional","affiliation":[{"name":"Department of Hematology and Rheumatology, Kindai University Faculty of Medicine; Osaka-sayama, Osaka 589-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/S1074-7613(00)80596-8","article-title":"Targeted disruption of the MyD88 gene results in loss of IL-1- and IL-18-mediated function","volume":"9","author":"Adachi","year":"1998","journal-title":"Immunity"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/S0167-5699(00)01611-X","article-title":"The IL-1 receptor\/toll-like receptor superfamily: Crucial receptors for inflammation and host defense","volume":"21","author":"Dinarello","year":"2000","journal-title":"Immunol. 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