Amelioration of antigen-induced arthritis in rats by transfer of extracellular superoxide dismutase and catalase genes

Extracellular superoxide dismutase (ecSOD) in vascular biology: an update on exogenous gene transfer and endogenous regulators of ecSOD

“…-associated oxidative stress by enhancing ecSOD has been applied successfully in various experimental disease models [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] (Table I). For example, ecSOD has been shown to restore erectile function in streptozotocin-induced diabetes, 33 protect against vascular dysfunction with aging, 19 blunt ischemia/reperfusion-induced liver injury, 32 reduce systemic vascular resistance and arterial pressure in spontaneously hypertensive rats, 21 improve endothelial dysfunction in hypertension and in heart failure models, 23,35 and ameliorate inflammatory arthritis.…”

“…For example, ecSOD has been shown to restore erectile function in streptozotocin-induced diabetes, 33 protect against vascular dysfunction with aging, 19 blunt ischemia/reperfusion-induced liver injury, 32 reduce systemic vascular resistance and arterial pressure in spontaneously hypertensive rats, 21 improve endothelial dysfunction in hypertension and in heart failure models, 23,35 and ameliorate inflammatory arthritis. 28,29 In most of the aforementioned studies, human ecSOD gene transfer was employed to augment ecSOD activity in animal models. Regarding the behavior and fate of the delivered foreign gene in recipient hosts, most studies showed an increase of ecSOD activity, with a corresponding decrease in levels, after gene transfer (Table I).…”

Infliximab Neutralizes the Suppressive Effect of TNF-&alpha; on Expression of Extracellular-Superoxide Dismutase <i>in Vitro</i>

“…The importance of EC-SOD has been explored in animal models of inflammatory arthritis: mice lacking EC-SOD presented more severe joint damage in collagen-induced arthritis, 27) whereas EC-SOD gene transfer in mice and rats suppressed the arthritis induced with collagen and antigen, respectively. 7,28) The destructive potential of TNF-a is mediated through activation of multiple intracellular signal transduction pathways. Among these molecules, p38 MAPK is considered to be one of the most important signals for TNF-a-mediated responses related to RA 29,30) and insulin resistance.…”

Gene therapy for arthritis

“…84,43,45 Therapeutic interventions to ameliorate the formation of free radicals, which mediate part cartilage and bone destruction via oxidative stress, include expression of extracellular superoxide dismutase (EC-SOD) from syngeneic fibroblasts 85 injected s.c. or in combination with catalase from immortalized syngeneic synoviocytes injected i.a. or s.c. 86 To inhibit matrix metalloproteinase (MMP) activity, TIMP-1 was expressed from an adenovirus vector injected i.v. 87 …”

“…86 These combination therapy studies indicated that targeting more than one pathway has synergistic if not at least additive clinical effects. New therapeutic targets are being discovered constantly including vasoactive intestinal peptide (VIP), 107 IL-17, 108 osteoprotegerin, 27 and IL-15 109 to name a few.…”