Increased expression of caspase-1 and interleukin-18 in peripheral blood mononuclear cells in patients with multiple sclerosis
Increased expression of caspase-1 and interleukin-18 in peripheral blood mononuclear cells in patients with multiple sclerosis
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DOI：
10.1191/1352458504ms1071oa
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发表时间：
2004-01-01
影响因子：
5.8
通讯作者：
Hillert, J
中科院分区：
文献类型：
--
作者：
Huang, WX;Huang, P;Hillert, J
多发性硬化（MS）被认为是中枢神经系统的T细胞介导的自身免疫性疾病。细胞因子和其他分子参与细胞凋亡的调节被认为是MS的发病机制的重要性。在这项研究中，白细胞介素18（IL-18），IL-1 β和他们的加工酶caspase-1的mRNA水平进行了定量的竞争性RT-PCR方法在未经刺激的外周血单核细胞（PBMC）在MS患者从未治疗疾病修饰药物。蛋白质印迹用于支持蛋白质水平的表达模式。我们发现，与健康对照组相比，MS患者中caspase-1和IL-18的表达显著增加。临床亚组分析显示，caspase-1在所有亚组中均升高，而IL-18在慢性进展（P = 0.001）和缓解期复发MS患者（P = 0.002）中上调，但在复发期间不显著（P = 0.12）。MS患者IL-1 β mRNA水平无显著变化，但慢性进展可能降低（P = 0.03）。IL-18表达的增加，可能在成熟蛋白水平上增加，可能表明在MS的未来治疗策略中值得考虑的途径。
Multiple sclerosis ( MS) is supposedly a T-cell mediated autoimmune disorder of the central nervous system. Cytokines and other molecules involved in the regulation of apoptosis are thought to be of importance for the pathogenesis of MS. In this study, the mRNA levels of interleukin 18 (IL-18), IL-1beta and their processing enzyme caspase-1 were quantified by a competitive RT-PCR method in unstimulated peripheral blood mononuclear cells (PBMCs) in MS patients never treated with disease modifying drugs. Western blot was used to support the expression pattern at the protein level. We found that the expression of caspase-1 and IL-18 was significantly increased in MS patients compared with healthy controls. Analysis of clinical subgroups revealed that caspase-1 was increased in all subgroups, whereas IL-18 was upregulated in chronic progression ( P = 0.001) and relapsing MS patients in remission ( P = 0.002) but not significantly during relapses ( P = 0.12). mRNA levels of IL-1beta were not significantly altered in MS except for a possible decrease in chronic progression ( P = 0.03). An increased IL-18 expression, potentially augmented at the mature protein level, may indicate a pathway worth considering in future therapeutic strategies in MS.