Therapeutic effects of TACI-Ig on collagen-induced arthritis by regulating T and B lymphocytes function in DBA/1 mice.
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.
Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immunopharmacology of Education Ministry of China, 230032 Hefei, PR China.
Yunjie
Y
Liu
Lingling
L
Zhang
Yingqi
Y
Wu
Tong
T
Tong
Wendi
W
Zhao
Peipei
P
Li
Min
M
Huang
Wenxiang
W
Wang
Jianmin
J
Fang
Wei
W
Wei
D000818:Animals; D001169:Arthritis, Experimental / Q000097:blood / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D015551:Autoimmunity / Q000187:drug effects; D053264:B-Cell Activating Factor / Q000097:blood; D016175:B-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D015232:Dinoprostone / Q000097:blood; D007596:Joints / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D011993:Recombinant Fusion Proteins / Q000494:pharmacology* / Q000627:therapeutic use; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology* / Q000473:pathology; D013950:Thymus Gland / Q000187:drug effects / Q000473:pathology
D053264:B-Cell Activating Factor; D011993:Recombinant Fusion Proteins; C524618:TACI receptor-IgG Fc fragment fusion protein; D015232:Dinoprostone