In vivo transfection of NFkappaB decoy significantly reduced the ratio of myocarditis-affected areas compared to scrambled decoy in rats with experimental autoimmune myocarditis.
Does NFkappaB decoy infusion reduce the severity of experimental autoimmune myocarditis in rats?
In vivo transfection of an NFkappaB decoy reduces the severity of experimental autoimmune myocarditis in rats, highlighting NFkappaB as a key regulator in disease progression.
Nuclear factor-kappaB (NFkappaB) plays a significant role in the coordinated transactivation of cytokine, inducible NO synthase (iNOS), and adhesion molecule genes. Although inflammation is an essential pathological feature of myocarditis, the role of NFkappaB in this process remains obscure. We examined the role of NFkappaB in the progression of rat experimental autoimmune myocarditis (EAM) and tested the hypothesis that NFkappaB blockade with a decoy against the cis element of NFkappaB can prevent the progression of EAM. Lewis rats were immunized with purified porcine cardiac myosin to establish EAM on day 0. NFkappaB decoy was infused into the rat coronary artery on day 0 (group NF0), 7 (group NF7), or 14 (group NF14) and harvested on day 21. Scrambled decoy was infused on day 0 (group SD0), 7 (group SD7), or 14 (group SD14) and served for control groups. The ratios of myocarditis-affected areas to the ventricular cross-sectional area of all treatment groups were significantly lower than those of the control groups (group NF0, 33+/-18% versus SD0, 53+/-14%; group NF7, 19+/-15% versus SD7, 50+/-16%; and group NF14, 34+/-10% versus SD14, 52+/-14%). Immunohistochemical and immunoblot analyses showed expression of ICAM-1, iNOS, IL-2, and TNFalpha in myocardium of scrambled decoy groups, and this expression was effectively suppressed by NFkappaB decoy treatment. Thus, we found that NFkappaB is a key regulator in the progression of EAM and that in vivo transfection of NFkappaB decoy reduces the severity of EAM.
Yokoseki et al. (Fri,) conducted a other in Experimental autoimmune myocarditis (EAM). NFkappaB decoy vs. Scrambled decoy was evaluated on Ratios of myocarditis-affected areas to the ventricular cross-sectional area. In vivo transfection of NFkappaB decoy significantly reduced the ratio of myocarditis-affected areas compared to scrambled decoy in rats with experimental autoimmune myocarditis.