Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Yushima, Bunkyo, Tokyo, Japan;
Am J Physiol Heart Circ Physiol. 2013 Dec;305(12):H1761-71. doi: 10.1152/ajpheart.00159.2013. Epub 2013 Oct 4.
NF-κB, which is activated by the inhibitor of NF-κB kinase (IKK), is involved in the progression of inflammatory disease. However, the effect of IKK inhibition on the progression of myocarditis is unknown. We examined the effect of IKK inhibition on the progression of myocarditis. Lewis rats were immunized with porcine cardiac myosin to induce experimental autoimmune myocarditis (EAM). We administered the IKK inhibitor (IMD-0354; 15 mg·kg(-1)·day(-1)) or vehicle to EAM rats daily. Hearts were harvested 21 days after immunization. Although the untreated EAM group showed increased heart weight-to-body weight ratio, and severe myocardial damage, these changes were attenuated in the IKK inhibitor-treated group. Moreover, IKK inhibitor administration significantly reduced NF-κB activation and mRNA expression of IFN-γ, IL-2, and monocyte chemoattractant protein-1 in myocardium compared with vehicle administration. In vitro study showed that the IKK inhibitor treatment inhibited T-cell proliferation and Th1 cytokines production induced by myosin stimulation. The IKK inhibitor ameliorated EAM by suppressing inflammatory reactions via suppression of T-cell activation.
NF-κB 可被 NF-κB 激酶抑制剂（IKK）激活，参与炎症性疾病的进展。然而，IKK 抑制对心肌炎进展的影响尚不清楚。我们研究了 IKK 抑制对心肌炎进展的影响。用猪心肌肌球蛋白免疫 Lewis 大鼠诱导实验性自身免疫性心肌炎（EAM）。我们每天给予 IKK 抑制剂（IMD-0354；15mg·kg(-1)·day(-1))或载体至 EAM 大鼠。免疫后 21 天收获心脏。虽然未治疗的 EAM 组显示出心脏重量/体重比增加和严重的心肌损伤，但在 IKK 抑制剂治疗组中这些变化得到了缓解。此外，与载体给药相比，IKK 抑制剂给药显著降低了心肌中 NF-κB 的激活和 IFN-γ、IL-2 和单核细胞趋化蛋白-1 的 mRNA 表达。体外研究表明，IKK 抑制剂通过抑制 T 细胞激活来抑制由肌球蛋白刺激诱导的 T 细胞增殖和 Th1 细胞因子的产生。IKK 抑制剂通过抑制 T 细胞激活改善了 EAM。
