Katoh N, Hirano S, Suehiro M, Ikenaga K, Yasuno H
Department of Dermatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Clin Exp Immunol. 2002 Feb;127(2):283-8. doi: 10.1046/j.1365-2249.2002.01740.x.
Matrix metalloproteinases and their specific inhibitors, tissue inhibitors of metalloproteinases (TIMPs), contribute to inflammation-induced tissue destruction and subsequent remodeling for maintenance of tissue homeostasis. Since the production of these enzymes and their inhibitors is regulated by mediators such as proinflammatory cytokines and growth factors, elevated levels of serum TIMPs and/or MMPs have been documented in patients with several inflammatory disorders. In this study, we examined the role of TIMPs and MMPs in the pathogenesis of atopic dermatitis (AD) by evaluating the serum levels of TIMP-1 and MMP-3 in 40 patients with AD and 20 control subjects by ELISA. The serum TIMP-1 levels were significantly higher in AD patients in exacerbation status than in nonatopic subjects, whereas serum MMP-3 levels were not significantly different between them. As a result, AD patients revealed significantly elevated TIMP-1/MMP-3 ratios. The levels of serum TIMP-1 were significantly reduced in AD patients following conventional treatments. Significantly higher values of peripheral eosinophil counts, serum levels of IgE and lactate dehydrogenase, eruption score, and eruption area were noted in the AD patients with elevated TIMP-1 levels when compared with those with normal values. Moreover, the points of chronic eruptions such as lichenification and prurigo were significantly higher in the patients with elevated TIMP-1 levels than those with normal TIMP-1, while those of acute lesions such as oozy/microvesicles and oedema were not different between these groups. Serum TIMP-1 level may be a useful marker to estimate the long-term disease activity of AD.
基质金属蛋白酶及其特异性抑制剂——金属蛋白酶组织抑制剂（TIMPs），参与炎症诱导的组织破坏以及随后的组织重塑，以维持组织稳态。由于这些酶及其抑制剂的产生受促炎细胞因子和生长因子等介质的调控，因此在患有多种炎症性疾病的患者中，血清TIMPs和/或MMPs水平升高已有文献记载。在本研究中，我们通过酶联免疫吸附测定法（ELISA）评估了40例特应性皮炎（AD）患者和20例对照者血清中TIMP-1和MMP-3的水平，以研究TIMPs和MMPs在AD发病机制中的作用。处于病情加重状态的AD患者血清TIMP-1水平显著高于非特应性受试者，而血清MMP-3水平在两者之间无显著差异。结果显示，AD患者的TIMP-1/MMP-3比值显著升高。常规治疗后，AD患者的血清TIMP-1水平显著降低。与TIMP-1水平正常的AD患者相比，TIMP-1水平升高的AD患者外周嗜酸性粒细胞计数、血清IgE和乳酸脱氢酶水平、皮疹评分及皮疹面积的值显著更高。此外，TIMP-1水平升高的患者慢性皮疹（如苔藓化和痒疹）的评分显著高于TIMP-1水平正常的患者，而急性皮损（如渗出/微水疱和水肿）的评分在两组之间无差异。血清TIMP-1水平可能是评估AD长期疾病活动度的有用指标。
