cis Element Decoy Against Nuclear Factor-κB Attenuates Development of Experimental Autoimmune Myocarditis in Rats

Abstract

Nuclear factor-κB (NFκB) 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 NFκB in this process remains obscure. We examined the role of NFκB in the progression of rat experimental autoimmune myocarditis (EAM) and tested the hypothesis that NFκB blockade with a decoy against the cis element of NFκB can prevent the progression of EAM. Lewis rats were immunized with purified porcine cardiac myosin to establish EAM on day 0. NFκB 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 TNFα in myocardium of scrambled decoy groups, and this expression was effectively suppressed by NFκB decoy treatment. Thus, we found that NFκB is a key regulator in the progression of EAM and that in vivo transfection of NFκB decoy reduces the severity of EAM.