Binding immunoglobulin protein resolves rheumatoid synovitis: A xenogeneic study using rheumatoid arthritis synovial membrane transplants in SCID mice

19Citations
Citations of this article
31Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

Introduction: 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 in vitro 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 in vivo model previously used to test the efficacy of biologic therapies.Methods: 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.Results: 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 TNFα 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.Conclusions: BiP has anti-inflammatory properties partially dependent on the downregulation of HLA-DR and co-stimulatory molecules and the predominant production of IL-10. © 2011 Yoshida et al.; licensee BioMed Central Ltd.

Cite

CITATION STYLE

APA

Yoshida, K., Ochiai, A., Matsuno, H., Panayi, G. S., & Corrigall, V. M. (2011). Binding immunoglobulin protein resolves rheumatoid synovitis: A xenogeneic study using rheumatoid arthritis synovial membrane transplants in SCID mice. Arthritis Research and Therapy, 13(5). https://doi.org/10.1186/ar3463

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free