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Therapeutic effects of TACI-Ig on collagen-induced arthritis by regulating T and B lymphocytes function in DBA/1 mice.

Abstract
To investigate the abnormal function of T and B lymphocytes involved in collagen-induced arthritis in DBA/1 mice and the regulation role of TACI-Ig on T and B lymphocytes, collagen-induced arthritis models were established in DBA/1 mice. Mice were divided randomly into eight groups, including normal, collagen-induced arthritis model, TACI-Ig (0.350, 1.105, 3.333, 10, and 30 mg/kg) and IgG-Fc (10mg/kg) treated groups. The effect of TACI-Ig on collagen-induced arthritis was evaluated by arthritis scores, joints and spleens histopathology, paws radiology, and indices of thymus and spleen. T and B lymphocyte proliferations were assayed by [(3)H]-TdR method. B lymphocyte stimulator and prostaglandin E(2) in serum were assayed by enzyme linked immunosorbent assay. The subsets of T and B lymphocytes were assayed by flow cytometry. Results showed that the onset of paw-swelling was on day 31 after immunization. The peak of inflammation appeared on day 42 and then declined after day 63. Compared with normal mice, collagen-induced arthritis mice have increased arthritis scores, spleen and thymus indices, radiograph scores of joints, and pathology scores of joints and spleens. TACI-Ig could ameliorate these changes and reduce the increased serum level of B lymphocyte stimulator and prostaglandin E(2). Further studies showed that TACI-Ig inhibited T and B lymphocyte proliferation response, and inhibited differentiation and activity of T and B lymphocytes in collagen-induced arthritis mice. In conclusion, TACI-Ig has a good therapeutic action on collagen-induced arthritis mice, which might be related to the regulation of TACI-Ig on inflammation mediators and abnormal function of T and B lymphocytes.
AuthorsYunjie Liu, Lingling Zhang, Yingqi Wu, Tong Tong, Wendi Zhao, Peipei Li, Min Huang, Wenxiang Wang, Jianmin Fang, Wei Wei
JournalEuropean journal of pharmacology (Eur J Pharmacol) Vol. 654 Issue 3 Pg. 304-14 (Mar 11 2011) ISSN: 1879-0712 [Electronic] Netherlands
PMID21244850 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2010 Elsevier B.V. All rights reserved.
Chemical References
  • B-Cell Activating Factor
  • Recombinant Fusion Proteins
  • TACI receptor-IgG Fc fragment fusion protein
  • Dinoprostone
Topics
  • Animals
  • Arthritis, Experimental (blood, drug therapy, immunology, pathology)
  • Autoimmunity (drug effects)
  • B-Cell Activating Factor (blood)
  • B-Lymphocyte Subsets (drug effects, immunology, pathology)
  • B-Lymphocytes (drug effects, immunology, pathology)
  • Cell Proliferation (drug effects)
  • Dinoprostone (blood)
  • Joints (drug effects, immunology, pathology)
  • Male
  • Mice
  • Recombinant Fusion Proteins (pharmacology, therapeutic use)
  • Spleen (drug effects, pathology)
  • T-Lymphocyte Subsets (drug effects, immunology, pathology)
  • T-Lymphocytes (drug effects, immunology, pathology)
  • Thymus Gland (drug effects, pathology)

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