scholarly journals Collagen-induced arthritis in mice. Localization of an arthritogenic determinant to a fragment of the type II collagen molecule.

1985 ◽  
Vol 162 (2) ◽  
pp. 637-646 ◽  
Author(s):  
K Terato ◽  
K A Hasty ◽  
M A Cremer ◽  
J M Stuart ◽  
A S Townes ◽  
...  

Purified chick type II collagen was cleaved with cyanogen bromide (CB), and the resulting peptides isolated and renatured. Sera from arthritic DBA/1 mice, immunized with chick type II collagen, were tested for reactivity with each peptide. The sera preferentially recognized peptides 11, 10, and 8, in that order. Some reactivity was also detected to peptides 9, 7, and 12. Because arthritis depends upon binding of antibody to autologous type II collagen in the joint, sera were also tested for reactivity with mouse type II collagen. There was a strong positive correlation between reactivity with peptide 11 and reactivity with mouse collagen, but no correlation was found with any of the other peptides. Peptides 11, 10, and 8 were also used for immunization. Antibodies were detected in response to each of these peptides, but arthritis developed only in mice immunized with peptide 11. We conclude that a major immunogenic and arthritogenic epitope on type II collagen resides in the region of the molecule represented by CB peptide 11.

2020 ◽  
Vol 9 (3) ◽  
Author(s):  
Ekaterina V. Gladkova

The aim of this research was to study the specifics of the matrix metallopeptidase system in early and late gonarthrosis (GA) manifestations. Material and Methods — 37 patients of the main group (0-I stages of GA), 30 patients of the comparison group (III-IV stages of GA) and 30 healthy individuals of the control group underwent sonography and T2-relaxometry of their knee joints. The 24-h excretion of urinary C-telopeptide fragments of type II collagen (СTX-II) as well as serum concentrations of matrix metalloproteinases-3 and -8 (MMP-3, MMP-8), and tissue inhibitor of metalloproteinases (TIMP-1) were also registered. Results — We detected increases in urinary СTX-II to 3.9 [2.5; 4.5] mg/d, MMP-8 to 364.7 [215; 434] pg/ml and TIMP-1 to 806 [559; 1157] pg/ml in the main group; to 9.7 [6.8; 10.2] mg/d, 579 [463; 663] pg/ml and 1256 [1029; 1330] pg/ml in the comparison group. The presence (p=0.04) of strong positive correlation (R=0.7) between the 24-h urinary СTX-II excretion and the change of MRI-signal characteristics for the areas of hyaline cartilage under the heaviest load on knee joints T2 relaxometry evidence was observed as well as the presence (p=0.001) of strong positive correlation (R=0.7) between MMP-8 and 24-h urinary СTX-II extraction. In early GA stages a strong positive correlation (R=0.6) was observed between MMP-8 and TIMP-1 (p=0.04) as well as 24-h urinary СTX-II excretion and TIMP-1 (R=0.5) at p˂0.001). Conclusion — Type II collagen degradation with MMP-8/TIMP-1 imbalance is one of the relevant mechanisms of the hyaline articular cartilage extracellular matrix disorganization in early and late GA evidences. The rearrangement of correlations between MMP-8 and TIMP-1 indicates the change in interaction mechanisms for GA proteolytic enzyme system components.


1989 ◽  
Vol 170 (6) ◽  
pp. 1999-2010 ◽  
Author(s):  
L K Myers ◽  
J M Stuart ◽  
J M Seyer ◽  
A H Kang

We have previously reported that collagen-induced arthritis can be suppressed by intravenous injection of native type II (CII) but not type I collagen. We have now identified denatured fragments of CII capable of suppressing collagen-induced arthritis and inducing tolerance. Purified CII was cleaved with cyanogen bromide (CB), and the major resulting peptides were isolated. Female DBA/1 mice were administered OVA, native CII, or one of the CB peptides, intravenously, before immunization with native CII, 6 wk after immunization, mice tolerized with CII and CB11 had a markedly lower incidence of arthritis compared with controls. There was a correlation between the overall antibody response and the incidence of arthritis. In addition, animals tolerized with either CII or CB11 had a decreased antibody response not only to CII, but also to each of the other CB peptides tested. To identify the epitope involved in suppression of arthritis, five synthetic peptides, 21-26 amino acids in length, corresponding to selected regions of CB11, were generated. Each of the peptides was injected intravenously into mice before immunization. Only one of these, CB11 122-147, was capable of suppressing arthritis. In addition, mice given the synthetic peptide CB11 122-147 neonatally were suppressed for arthritis and antibody responsiveness when immunized with CII at 8 wk of age. Thus, we have identified CB11 122-147 as an epitope of CII important in induction of tolerance and suppression of disease. Further experiments narrowing down the pivotal amino acids for the immunogenicity of this epitope and the role this epitope plays in induction and regulation of disease will enhance our understanding of how the immune response to collagen affects autoimmune arthritis.


1995 ◽  
Vol 17 (7) ◽  
pp. 597-603 ◽  
Author(s):  
Makoto Ueno ◽  
Kazunori Imaizumi ◽  
Takahisa Sugita ◽  
Isao Takata ◽  
Masakazu Takeshita

2010 ◽  
Vol 31 (5) ◽  
pp. 595-603 ◽  
Author(s):  
Samjin Choi ◽  
Yeon-Ah Lee ◽  
Seung-Jae Hong ◽  
Gi-Ja Lee ◽  
Sung Wook Kang ◽  
...  

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Corina Peña ◽  
David Gárate ◽  
Juan Contreras-Levicoy ◽  
Octavio Aravena ◽  
Diego Catalán ◽  
...  

Background. Pharmacologically modulated dendritic cells (DCs) have been shown to restore tolerance in type II collagen-(CII-) induced arthritis (CIA). We examined the effect of dexamethasone (DXM) administration as a preconditioning agent, followed by an injection of lipopolysaccharide-(LPS-) stimulated and CII-loaded DCs on the CIA course.Methods. After CIA induction, mice pretreated with DXM were injected with 4-hour LPS-stimulated DCs loaded with CII (DXM/4hLPS/CII/DCs).Results. Mice injected with DXM/4hLPS/CII/DCs displayed significantly less severe clinical disease compared to animals receiving 4hLPS/CII/DCs alone or those in which only DXM was administered. Cytokine profile evaluation showed that CD4+ T cells from DXM/4hLPS/CII/DCs and 4hLPS/CII/DCs groups release higher IL-10 levels than those from mice receiving DXM alone or CIA mice. CD4+ T cells from all DC-treated groups showed less IL-17 release when compared to the CIA group. On the contrary, CD4+ T cells from DXM/4hLPS/CII/DCs and 4hLPS/CII/DCs groups released higher IFN-γlevels than those from CIA group.Conclusion. A combined treatment, including DXM preconditioning followed by an inoculation of short-term LPS-stimulated CII-loaded DCs, provides an improved strategy for attenuating CIA severity. Our results suggest that this benefit is driven by a modulation in the cytokine profile secreted by CD4+ T cells.


2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Zhi-Dan Fan ◽  
Ya-Yuan Zhang ◽  
Yi-Hong Guo ◽  
Na Huang ◽  
Hui-Hui Ma ◽  
...  

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