Hydroxyl Radical Modification of Collagen Type II Increases Its Arthritogenicity and Immunogenicity
نویسندگان
چکیده
BACKGROUND The oxidation of proteins by endogenously generated free radicals causes structural modifications in the molecules that lead to generation of neo-antigenic epitopes that have implications in various autoimmune disorders, including rheumatoid arthritis (RA). Collagen induced arthritis (CIA) in rodents (rats and mice) is an accepted experimental model for RA. METHODOLOGY/PRINCIPAL FINDINGS Hydroxyl radicals were generated by the Fenton reaction. Collagen type II (CII) was modified by •OH radical (CII-OH) and analysed by ultraviolet-visible (UV-VIS), fluorescence and circular dichroism (CD) spectroscopy. The immunogenicity of native and modified CII was checked in female Lewis rats and specificity of the induced antibodies was ascertained by enzyme linked immunosorbent assay (ELISA). The extent of CIA was evaluated by visual inspection. We also estimated the oxidative and inflammatory markers in the sera of immunized rats. A slight change in the triple helical structure of CII as well as fragmentation was observed after hydroxyl radical modification. The modified CII was found to be highly arthritogenic and immunogenic as compared to the native form. The CII-OH immunized rats exhibited increased oxidative stress and inflammation as compared to the CII immunized rats in the control group. CONCLUSIONS/SIGNIFICANCE Neo-antigenic epitopes were generated on (•)OH modified CII which rendered it highly immunogenic and arthritogenic as compared to the unmodified form. Since the rodent CIA model shares many features with human RA, these results illuminate the role of free radicals in human RA.
منابع مشابه
Arthritis induced in rats by cloned T lymphocytes responsive to mycobacteria but not to collagen type II.
We have been studying the pathogenesis of adjuvant arthritis in rats using a long-term cell line of T lymphocytes, the A2 line, which can induce polyarthritis and can also be used to vaccinate rats against adjuvant arthritis. Although line A2 was selected for its proliferative response to mycobacteria, it also responded to collagen type II. To elucidate its role of responsiveness to collagen ty...
متن کاملCitrullinated proteins have increased immunogenicity and arthritogenicity and their presence in arthritic joints correlates with disease severity
Autoantibodies directed against citrulline-containing proteins have an impressive specificity of nearly 100% in patients with rheumatoid arthritis and have been suggested to be involved in the disease pathogenesis. The targeted epitopes are generated by a post-translational modification catalysed by the calcium-dependent enzyme peptidyl arginine deiminase (PAD), which converts positively charge...
متن کاملExpression of Collagen Type II and Osteocalcin Genes in Mesenchymal Stem Cells from Rats Treated with Lead acetate II
Background: Lead is one of the sustainable metals with devastating effects on many tissues. This study, examined the adverse effect of lead poisoning on the gene expression of collagen type II and osteocalcin by mesenchymal stem cells (MSCs) cultured in chondrogenic and osteogenic media, respectively. Methods: We used 18 male Wistar rats, divided in 3 groups. In addition to libitum feed as the...
متن کاملEffects of copper and histidine on oxidative modification of low density lipoprotein and its subsequent binding to collagen.
It was previously shown that serum low density lipoprotein (LDL) binds to type I collagen gels and that the binding is increased after modification by cultured endothelial cells. It is now demonstrated that when LDL is incubated with cells cultured in Dulbecco's modified minimal essential medium (DMEM), the subsequent binding of LDL to collagen is considerably less than after incubation with en...
متن کامل