Orbán Csaba, Szabó Dolóresz, Bajnok Anna, Vásárhelyi Barna, Tulassay Tivadar, Arató András, Veres Gábor, Toldi Gergely
First Department of Pediatrics, Semmelweis University, Budapest, Hungary.
Department of Dietetics and Nutrition Sciences, Faculty of Health Sciences, Semmelweis University, Budapest, Hungary.
Oncotarget. 2016 Jul 19;7(29):44966-44974. doi: 10.18632/oncotarget.10036.
Crohn's disease is a chronic inflammation of the gastrointestinal tract with an abnormal immune phenotype. We investigated how intracellular calcium kinetics of Th1 and Th2 lymphocytes alter upon specific inhibition of Kv1.3 and IKCa1 channels in pediatric Crohn's disease.
Blood was taken from 12 healthy and 29 Crohn's disease children. Of those, 6 were switched to infliximab and re-sampled after the 4th infliximab treatment. Intracellular calcium levels were monitored using flow cytometry in the presence or absence of specific inhibitors of Kv1.3 and IKCa1 potassium channels.
In Crohn's disease treated with standard therapy, calcium response during activation was higher than normal in Th2 cells. This was normalized in vitro by inhibition of Kv1.3 or IKCa1 potassium channels. After the switch to infliximab, potassium channel function and expression in Th2 lymphocytes were comparable to those in Th1 cells.
These results may indicate that potassium channels are potential immune modulatory targets in Crohn's disease.
克罗恩病是一种具有异常免疫表型的胃肠道慢性炎症。我们研究了在儿童克罗恩病中，特异性抑制Kv1.3和IKCa1通道后，Th1和Th2淋巴细胞的细胞内钙动力学如何改变。
采集了12名健康儿童和29名克罗恩病儿童的血液。其中，6名患儿改用英夫利昔单抗治疗，并在第4次英夫利昔单抗治疗后重新采样。在存在或不存在Kv1.3和IKCa1钾通道特异性抑制剂的情况下，使用流式细胞术监测细胞内钙水平。
在接受标准治疗的克罗恩病中，Th2细胞激活期间的钙反应高于正常水平。通过抑制Kv1.3或IKCa1钾通道，在体外可使其恢复正常。改用英夫利昔单抗后，Th2淋巴细胞中的钾通道功能和表达与Th1细胞相当。
这些结果可能表明钾通道是克罗恩病潜在的免疫调节靶点。
