{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T10:26:06Z","timestamp":1766485566659},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2012,7,6]],"date-time":"2012-07-06T00:00:00Z","timestamp":1341532800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,7,6]]},"abstract":"<jats:title>Summary<\/jats:title>\n               <jats:p>This study is investigating the role of leukaemia inhibitory factor (LIF) in the development of inflammation and joint damage in the mouse K\/B\u00d7N serum transfer arthritis model. LIF knock-out (LIF\u2212\/\u2212) mice were generated by mating heterozygote females (LIF+\/\u2212) with heterozygote males. Arthritis was induced in 8\u201320-week-old LIF knock-out mice (LIF\u2212\/\u2212) by intraperitoneal injection of pooled K\/B\u00d7N sera (50\u2003\u00b5l) on days 0 and 2. Clinical disease was scored daily for 6 days. Safranin-O and haematoxylin-stained sections were scored for synovitis, joint space exudate, cartilage degradation and bone damage. RNA was extracted from ankle joints and used to investigate gene expression levels of tumour necrosis factor (TNF)-\u03b1, interleukin (IL)-1, LIF, LIF receptor, oncostatin M (OSM), OSM receptor, IL-6 and their common receptor subunit gp130 by quantitative reverse transcription\u2013polymerase chain reaction (qRT\u2013PCR). The results show that wild-type mice developed severe clinically overt polyarthritis. In contrast, LIF\u2212\/\u2212 mice showed a more than 50% reduction in clinical arthritis severity. Significantly lower histological scores were observed in LIF\u2212\/\u2212 mice compared to wild-type disease controls. LIF\u2212\/\u2212 mice had histopathological scores that were similar to normal healthy mice. IL-6 subfamily cytokine and receptor subunit expression remained unchanged. The expression levels for IL-6 were reduced significantly in all the diseased mice, whether wild-type or LIF\u2212\/\u2212 mice (P\u2003&amp;lt;\u20030\u00b7001), compared to healthy wild-type mice. We conclude that LIF contributes to the development of disease in the K\/B\u00d7N serum transfer model of arthritis. These results provide further evidence for the role of LIF in inflammation and cartilage bone resorption and provide impetus to test the effects of LIF blockade as a therapeutic strategy in rheumatoid arthritis.<\/jats:p>","DOI":"10.1111\/j.1365-2249.2012.04601.x","type":"journal-article","created":{"date-parts":[[2012,4,25]],"date-time":"2012-04-25T10:41:52Z","timestamp":1335350512000},"page":"71-78","source":"Crossref","is-referenced-by-count":10,"title":["K\/B\u00d7N serum transfer arthritis is delayed and less severe in leukaemia inhibitory factor (LIF)-deficient mice"],"prefix":"10.1093","volume":"169","author":[{"given":"A","family":"Upadhyay","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Biology, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D","family":"Senyschyn","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biology, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L","family":"Santos","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine, University College Dublin, Dublin, Republic of Ireland"},{"name":"Centre for Inflammatory Diseases, Monash Medical Centre, Clayton, Vic."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R","family":"Gu","sequence":"additional","affiliation":[{"name":"Centre for Inflammatory Diseases, Monash Medical Centre, Clayton, Vic."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G J","family":"Carroll","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Fremantle Hospital"},{"name":"School of Medicine, University of Notre Dame Australia (Fremantle), Fremantle"},{"name":"School of Medicine and Pharmacology, University of Western Australia, Perth, WA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J A","family":"Jazayeri","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biology, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville"},{"name":"School of Biomedical Sciences, Charles Sturt University, Wagga Wagga, NSW, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2012,7,6]]},"reference":[{"key":"2021122708375621200_b1","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1046\/j.1365-3083.1998.00399.x","article-title":"Synovial fluid cytokines in patients with rheumatoid arthritis or other arthritic lesions","volume":"48","author":"Lettesjo","year":"1998","journal-title":"Scand J Immunol"},{"key":"2021122708375621200_b2","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1038\/nri802","article-title":"Development of anti-TNF therapy for rheumatoid 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