Prevention of collagen-induced arthritis in mice transgenic for the complement inhibitor complement receptor 1-related gene/protein y.
The objective of these studies was to examine collagen-induced arthritis (CIA) in C57BL/6 mice transgenic for the rodent complement regulatory protein complement receptor 1-related gene/protein y (Crry) (Crry-Tg), a C3 convertase inhibitor. The scores for clinical disease activity and for histological damage in the joints were both significantly decreased in Crry-Tg mice in comparison to wild-type (WT) littermates. The production of both IgG1 and IgG2a anti-collagen Abs was reduced in the Crry-Tg mice, although spleen cell proliferation in response to collagen type II was not altered. The production of IFN-gamma, TNF-alpha, and IL-1beta by LPS-stimulated spleen cells was decreased, and IL-10 was increased, in cells from Crry-Tg mice in comparison to WT. The steady-state mRNA levels for IFN-gamma, TNF-alpha, and IL-1beta were all decreased in the joints of Crry-Tg mice in comparison to WT. The synovium from Crry-Tg mice without CIA contained the mRNA for the Crry transgene, by RT-PCR, and the synovium from transgenic mice with CIA exhibited little deposition of C3 protein by immunohistological analysis. These results suggest that suppression of CIA in Crry-Tg mice may be due to enhanced synthesis of Crry locally in the joint with decreased production of proinflammatory cytokines.
Banda
Nirmal K
NK
Division of Rheumatology, University of Colorado Health Sciences Center, Denver, CO 80262. BolderPATH, Boulder, CO 80309, USA.
Kraus
Damian M
DM
Muggli
Michele
M
Bendele
Alison
A
Holers
V Michael
VM
Arend
William P
WP
D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D001323:Autoantibodies / Q000096:biosynthesis / Q000097:blood; D002417:Cattle; D024043:Collagen Type II / Q000008:administration & dosage / Q000276:immunology*; D003169:Complement Inactivator Proteins / Q000235:genetics*; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006614:Hindlimb; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D007150:Immunohistochemistry; D007271:Injections, Intradermal; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics; D016131:Lymphocyte Subsets / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000032:analysis; D011951:Receptors, Complement / Q000096:biosynthesis / Q000235:genetics*; D017463:Receptors, Complement 3b / Q000235:genetics*; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism
D001323:Autoantibodies; D024043:Collagen Type II; D003169:Complement Inactivator Proteins; C081470:Cr1l protein, mouse; D016207:Cytokines; D007074:Immunoglobulin G; D012333:RNA, Messenger; D011951:Receptors, Complement; D017463:Receptors, Complement 3b