Reactive oxygen species (ROS), but not nitric oxide (NO), contribute to strain differences in the susceptibility to experimental arthritis in rats.
ABSTRACT There is extensive evidence for the critical role of reactive oxygen species (ROS) and nitric oxide (NO) produced by phagocytes in development of inflammatory processes and pathogenesis of numerous diseases, including rheumatoid arthritis (RA). Apart from their function as mediators of inflammation and tissue damage, recent research supports their role as signaling and regulatory molecules. In the present study we have investigated the production of ROS and NO over the course of adjuvant arthritis (AA) and oil-induced arthritis (OIA), by resident peritoneal macrophages of two rat strains: Dark Agouti (DA), susceptible, and Albino Oxford (AO), resistant to induction of AA and OIA. We have compared levels of ROS and NO produced by susceptible vs. resistant rat strain, and investigated their relevancy for arthritis development and severity. In addition, we have stimulated macrophages in vitro with Mycobacterium bovis BCG, and two heat shock proteins (HSP): endogenous HSP47 and mycobacterial HSP71 (mHSP71). Our results suggest a possible contribution of increased ROS production to arthritis resistance of AO rats. The ROS production in AO rats is potentiated by endogenous HSP47, but not with mycobacterial cell and mHSP71, suggesting HSP47 participates in AA control. We have found no fundamental relationship between the magnitude of NO production and AA and OIA susceptibility and severity, suggesting that NO has no effector role in AA and OIA. Our results advocate a regulatory type action of NO molecule might be more significant in arthritis development.
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ABSTRACT: Adjuvant arthritis (AA) serves as an excellent model for human rheumatoid arthritis. AA is readily inducible in certain rat strains, but not in others. Susceptibility/resistance to AA is determined by multiple factors. Among the genetic factors, both MHC and non-MHC genes contribute to arthritis susceptibility, and specific quantitative trait loci show association with the severity of the disease. Differential T-cell proliferative and cytokine responses, as well as antibody responses, to heat-shock proteins are evident when comparing AA-susceptible and AA-resistant rats. In addition, neuroendocrine factors and the housing environment can further modulate arthritis susceptibility/severity in particular rat strains.Arthritis research & therapy 09/2009; 11(4):239. · 4.27 Impact Factor
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ABSTRACT: Arthritis was induced in 9-week-old female Dark Agouti rats by injecting type II collagen. Serum levels of the derivatives of reactive oxygen metabolites (dROMs), which are oxidative stress markers, and C-reactive protein (CRP) in arthritic rats that were exposed to a pressure of 1.25 atmospheres absolute and an oxygen concentration of 36% for 3 weeks (arthritis + HBO group) were compared to those of control rats (control group) and arthritic rats that were not exposed to hyperbaric oxygen (arthritis group). The body weights of the arthritis and arthritis + HBO groups were lower than that of the control group, whereas no difference in the body weight was observed between the arthritis and arthritis + HBO groups. The serum levels of dROMs and CRP in the arthritis group were higher than those in the control and arthritis + HBO groups. No difference in the serum level of CRP was observed between the control and arthritis + HBO groups. These results indicate that the conditions of hyperbaric oxygen exposure used in this study are effective for reducing the levels of reactive oxygen species, which are overproduced during arthritis.Clinical and Experimental Medicine 09/2009; · 2.40 Impact Factor
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ABSTRACT: Much evidence has identified a direct anatomical and functional link between the brain and the immune system, with glucocorticoids (GCs), catecholamines (CAs), and neuropeptide Y (NPY) as its end-point mediators. This suggests the important role of these mediators in immune system homeostasis and the pathogenesis of inflammatory autoimmune diseases. However, although it is clear that these mediators can modulate lymphocyte maturation and the activity of distinct immune cell types, their putative role in the pathogenesis of autoimmune disease is not yet completely understood. We have contributed to this field by discovering the influence of CAs and GCs on fine-tuning thymocyte negative selection and, in particular, by pointing to the putative CA-mediated mechanisms underlying this influence. Furthermore, we have shown that CAs are implicated in the regulation of regulatory T-cell development in the thymus. Moreover, our investigations related to macrophage biology emphasize the complex interaction between GCs, CAs and NPY in the modulation of macrophage functions and their putative significance for the pathogenesis of autoimmune inflammatory diseases.Immunologic Research 03/2012; 52(1-2):64-80. · 2.96 Impact Factor