cis element decoy against nuclear factor-kappa B attenuates development ofexperimental autoimmune myocarditis in rats

Nuclear factor-kappaB (NF kappaB) plays a significant role in the coordinat ed transactivation of cytokine, inducible NO synthase (iNOS), and adhesion molecule genes. Although inflammation is an essential pathological feature of myocarditis, the role of NF kappaB in this process remains obscure. We e xamined the role of NF kappaB in the progression of rat experimental autoin imune myocarditis (EAM) and tested the hypothesis that NF kappaB blockade w ith a decoy against the cis element of NF kappaB can prevent the progressio n of EAM. Lewis rats were immunized with purified porcine cardiac myosin to establish EAM on day 0. NF kappaB decoy was infused into the rat coronary artery on day 0 (group NF0), 7 (group NF7), or 14 (group NF14) and harveste d 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 myocardi tis-affected areas to the ventricular cross-sectional area of all treatment groups were significantly lower than those of the control groups (group NF O, 33 +/- 18% versus SD0, 53 +/- 14%;. group NF7, 19 +/- 15% versus SD7, 50 +/- 16%; and group NF14, 34 +/- 10% versus SD14, 52 +/- 14%). Immunohistoc hemical and immunoblot analyses showed expression of ICAM-1, iNOS, IL-2, an d TNF alpha in myocardium of scrambled decoy groups, and this expression wa s effectively suppressed by NF kappaB decoy treatment. Thus, we found that NF kappaB is a key regulator in the progression of EAM and that in vivo tra nsfection of NF kappaB decoy reduces the severity of EAM.