Cathepsins and their endogenous inhibitors cystatins: expression and modulation in multiple sclerosis.
Cathepsins and their endogenous inhibitors cystatins: expression and modulation in multiple sclerosis.
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DOI：
10.1111/j.1582-4934.2010.01229.x
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发表时间：
2011-11
影响因子：
5.3
通讯作者：
Miller A
中科院分区：
文献类型：
--
作者：
Haves-Zburof D;Paperna T;Gour-Lavie A;Mandel I;Glass-Marmor L;Miller A
组织蛋白酶参与多种生理过程，包括抗原加工和呈递以及细胞外基质降解。在本研究中，我们评估了组织蛋白酶S和B及其抑制剂半胱氨酸蛋白酶抑制剂B和C的表达水平是否受多发性硬化（MS）疾病状态（复发和缓解）和治疗（干扰素-β[IFN-β]和糖皮质激素[GC]甲基强的松龙）的影响，以及它们是否与IFN-β反应表型相关。采用Real-time PCR方法检测MS患者和正常对照组外周血白细胞RNA表达水平，ELISA方法检测MS患者和正常对照组血清蛋白水平。与对照组相比，复发状态的MS患者的组织蛋白酶S RNA更高（74%，P= 3 × 10−5，n= 30 vs n= 18），血清中观察到类似的升高（66%，P= 0.002，n= 18 vs n= 20）。GC处理降低PBL RNA中的组织蛋白酶S水平（44%，P= 6 × 10−6，n= 27）和血清蛋白（降低27%，P= 1 × 10−5，n= 26），降低组织蛋白酶原B的血清蛋白水平（8%，P= 0.0007，n= 23），并平行增加其抑制剂胱抑素C的血清水平（82%，P= 8 × 10−6，n= 26）。IFN-β治疗显著提高了组织蛋白酶B（16%，P= 0.03）、胱抑素B（44%，P= 0.004）和胱抑素C（48%，P= 0.011）的RNA水平（n= 16）。在血清中，IFN-β仅降低组织蛋白酶S水平（16%，P= 0.006，n= 25）。有趣的是，与没有良好反应的患者相比，对IFN-β治疗“良好反应者”的治疗前血清组织蛋白酶S/半胱氨酸蛋白酶C比率较高（94%，P= 0.003）。这些结果表明，组织蛋白酶S和半胱氨酸蛋白酶抑制剂C可能有助于MS的疾病活动，特别是在对IFN-β治疗有反应的患者亚组中，并且这些蛋白质应作为MS的生物标志物进行进一步评价。
Cathepsins are involved in a variety of physiological processes including antigen processing and presentation and extracellular matrix degradation. In the present study, we evaluated whether expression levels of cathepsins S and B and their inhibitors cystatins B and C are affected by multiple sclerosis (MS) disease state (relapse and remission) and therapies (interferon-β[IFN-β] and the glucocorticoid [GC] methylprednisolone), and whether they are associated with the IFN-β response phenotype. Real-time PCR was employed to compare RNA expression levels in peripheral blood leucocytes (PBLs) and ELISA to determine serum protein levels of MS patients and matched healthy individuals. Cathepsin S RNA was higher in MS patients in the relapse state compared to controls (by 74%, P= 3 × 10−5, n= 30 versus n= 18) with a similar increase observed in serum (66%, P= 0.002, n= 18 versus n= 20). GC treatment reduced cathepsin S levels in PBL RNA (by 44%, P= 6 × 10−6, n= 27) and serum proteins (by 27%, P= 1 × 10−5, n= 26), reduced the serum protein levels of pro-cathepsin B (by 8%, P= 0.0007, n= 23), and in parallel increased the serum levels of their inhibitor cystatin C (by 82%, P= 8 × 10−6, n= 26). IFN-β therapy significantly elevated the RNA levels (n= 16) of cathepsin B (by 16%, P= 0.03), cystatin B (44%, P= 0.004) and cystatin C (48%, P= 0.011). In the serum, only cathepsin S levels were reduced by IFN-β (16%, P= 0.006, n= 25). Interestingly, pre-treatment serum cathepsin S/cystatin C ratio was higher in ‘good responders’ to IFN-β therapy compared to patients without a good response (by 94%, P= 0.003). These results suggest that cathepsin S and cystatin C may contribute to disease activity in MS, specifically in a subgroup of patients that are responsive to IFN-β therapy, and that these proteins should be further evaluated as biomarkers in MS.
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影响因子：
11
作者：
Glass-Marmor, Lea;Paperna, Tamar;Miller, Ariel
通讯作者：
Miller, Ariel
影响因子：
6
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14.5
作者：
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影响因子：
11.2
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影响因子：
4.3
作者：
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通讯作者：
Joyce, Johanna A.