{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T17:49:09Z","timestamp":1778953749581,"version":"3.51.4"},"reference-count":15,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2011,9,14]],"date-time":"2011-09-14T00:00:00Z","timestamp":1315958400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"},{"start":{"date-parts":[[2011,9,14]],"date-time":"2011-09-14T00:00:00Z","timestamp":1315958400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arthritis Res Ther"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                        <jats:title>Introduction\n<\/jats:title>\n                        <jats:p>Binding immunoglobulin protein (BiP) has previously shown powerful anti-inflammatory properties in the collagen-induced arthritis (CIA) model, where a single dose of BiP has proved to be both a long-term prophylactic and therapeutic. In both CIA and human <jats:italic>in vitro<\/jats:italic> studies, BiP induced regulatory T cells. The present investigation looked at the anti-inflammatory effect of BiP on inflamed human synovial tissue transplanted into severe combined immunodeficient mice (SCID), a chimaeric <jats:italic>in vivo<\/jats:italic> model previously used to test the efficacy of biologic therapies.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Methods\n<\/jats:title>\n                        <jats:p>Rheumatoid arthritis synovial membrane (RASM) was engrafted into SCID mice. Following successful engraftment, mice were intravenously injected with BiP or human serum albumin in the presence or absence of anti-IL-10 mAb. Twelve days later the grafts were removed for analysis and human cytokines in the sera were quantified by ELISA. The extent of residual inflammatory cellular infiltrate in the synovial explants was determined by weight of the explants.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results\n<\/jats:title>\n                        <jats:p>The RASM transplants from mice treated with BiP showed visual reduction in cellular infiltrate and downregulation of all quantifiable features of inflammation as assessed by the Koizumi or Rooney histological criteria. Also downregulated were HLA-DR, CD86, IL-6 and TNF\u03b1 expression as assessed by immunohistology. ELISA detected significantly less human IL-6 circulating in the BiP-treated mouse serum. After removal of transplanted tissue 12 days post administration of BiP, the RASM explants from the BiP-treated SCID mice weighed significantly less, indicating a suppression of tissue inflammation. Mice given concomitant neutralising anti-IL-10 antibody and BiP showed no such suppression.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusions\n<\/jats:title>\n                        <jats:p>BiP has anti-inflammatory properties partially dependent on the downregulation of HLA-DR and co-stimulatory molecules and the predominant production of IL-10.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/ar3463","type":"journal-article","created":{"date-parts":[[2011,9,14]],"date-time":"2011-09-14T06:55:43Z","timestamp":1315983343000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Binding immunoglobulin protein resolves rheumatoid synovitis: a xenogeneic study using rheumatoid arthritis synovial membrane transplants in SCID mice"],"prefix":"10.1186","volume":"13","author":[{"given":"Kaoru","family":"Yoshida","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akira","family":"Ochiai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroaki","family":"Matsuno","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriel S","family":"Panayi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valerie M","family":"Corrigall","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2011,9,14]]},"reference":[{"key":"3218_CR1","doi-asserted-by":"publisher","first-page":"1164","DOI":"10.1002\/art.20134","volume":"50","author":"VM Corrigall","year":"2004","unstructured":"Corrigall VM, Bodman-Smith MD, Brunst M, Cornell H, Panayi GS: The stress protein, BiP, stimulates human peripheral blood mononuclear cells to express an anti-inflammatory cytokine profile and to inhibit antigen presenting cell function: relevance to the treatment of inflammatory arthritis. Arthritis Rheum. 2004, 50: 1164-1171. 10.1002\/art.20134.","journal-title":"Arthritis Rheum"},{"key":"3218_CR2","doi-asserted-by":"publisher","first-page":"854","DOI":"10.1002\/art.21654","volume":"54","author":"RJ Brownlie","year":"2006","unstructured":"Brownlie RJ, Myers LK, Wooley PH, Corrigall VM, Bodman-Smith MD, Panayi GS, Thompson SJ: Treatment of murine collagen-induced arthritis by the stress protein BiP via interleukin-4-producing regulatory T cells: a novel function for an ancient protein. Arthritis Rheum. 2006, 54: 854-863. 10.1002\/art.21654.","journal-title":"Arthritis Rheum"},{"key":"3218_CR3","doi-asserted-by":"publisher","first-page":"976","DOI":"10.1136\/ard.2009.126573","volume":"69","author":"JL Nam","year":"2010","unstructured":"Nam JL, Winthrop KL, van Vollenhoven RF, Pavelka K, Valesini G, Hensor EM, Worthy G, Landew\u00e9 R, Smolen JS, Emery P, Buch MH: Current evidence for the management of rheumatoid arthritis with biological disease-modifying antirheumatic drugs: a systematic literature review informing the EULAR recommendations for the management of RA. Ann Rheum Dis. 2010, 69: 976-986. 10.1136\/ard.2009.126573.","journal-title":"Ann Rheum Dis"},{"key":"3218_CR4","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1093\/rheumatology\/41.3.329","volume":"41","author":"H Matsuno","year":"2002","unstructured":"Matsuno H, Yudoh K, Katayama R, Nakazawa F, Uzuki M, Sawai T, Yonezawa T, Saeki Y, Panayi GS, Pitzalis C, Kimura T: The role of TNF-\u03b1 in the pathogenesis of inflammation and joint destruction in rheumatoid arthritis (RA): a study using a human RA\/SCID mouse chimera. 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Arthritis Rheum. 1998, 41: 2014-2021. 10.1002\/1529-0131(199811)41:11<2014::AID-ART17>3.0.CO;2-T.","journal-title":"Arthritis Rheum"},{"key":"3218_CR6","doi-asserted-by":"publisher","first-page":"1492","DOI":"10.4049\/jimmunol.166.3.1492","volume":"166","author":"VM Corrigall","year":"2001","unstructured":"Corrigall VM, Bodman-Smith MD, Fife MS, Canas B, Myers LK, Wooley PH, Soh C, Staines NJ, Pappin DJC, Berlo SE, van Eden W, van der Zee R, Lanchbury JS, Panayi GS: The human endoplasmic reticulum molecular chaperone BiP is an autoantigen for rheumatoid arthritis and prevents the induction of experimental arthritis. J Immunol. 2001, 166: 1492-1498.","journal-title":"J Immunol"},{"key":"3218_CR7","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1046\/j.1440-1827.1999.00863.x","volume":"49","author":"F Koizumi","year":"1998","unstructured":"Koizumi F, Matsuno H, Wakaki K, Ishii Y, Kurashige Y, Nakamura H: Synovitis in rheumatoid arthritis: scoring of characteristic histopathological features. Pathol Int. 1998, 49: 298-304.","journal-title":"Pathol Int"},{"key":"3218_CR8","doi-asserted-by":"publisher","first-page":"956","DOI":"10.1002\/art.1780310803","volume":"31","author":"M Rooney","year":"1988","unstructured":"Rooney M, Condell D, Quinlan W, Daly L, Whelan A, Feighery C, Bresnihan B: Analysis of the histologic variation of synovitis in rheumatoid arthritis. 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