title: 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.
authors.affiliation: Immunology Research Center Branislav Janković, Institute of Immunology and Virology Torlak, Vojvode Stepe 458, 11121 Belgrade, Serbia.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Miletić
authors.forename: Vesna
authors.initials: V
authors.lastname: Kovacević-Jovanović
authors.forename: Vesna
authors.initials: V
authors.lastname: Vujić
authors.forename: Stanislava
authors.initials: S
authors.lastname: Stanojević
authors.forename: Katarina
authors.initials: K
authors.lastname: Mitić
authors.forename: Mirjana
authors.initials: M
authors.lastname: Lazarević-Macanović
authors.forename: Mirjana
authors.initials: M
authors.lastname: Dimitrijević
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics / Q000378:metabolism*; D020022:Genetic Predisposition to Disease; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013045:Species Specificity
chemical_list: D017382:Reactive Oxygen Species; D009569:Nitric Oxide