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首页> 外文期刊>Allergy >German cockroach proteases regulate matrix metalloproteinase-9 in human bronchial epithelial cells.
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German cockroach proteases regulate matrix metalloproteinase-9 in human bronchial epithelial cells.

机译：德国蟑螂蛋白酶调节人支气管上皮细胞中的基质金属蛋白酶9。

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BACKGROUND: Matrix metalloproteinases (MMPs) digest extracellular matrix proteins and may play a role in the pathogenesis of bronchial asthma. MMP-9 levels are increased in the bronchoalveolar lavage fluid and sputum of asthmatics compared with that of controls. As exposure to cockroaches is an environmental risk factor for asthma, we sought to investigate the role of German cockroach fecal remnants (frass) on MMP-9 expression. METHODS: Human bronchial epithelial cells (16HBE14o-) and primary normal human bronchial epithelial cells were treated with cockroach frass in the absence or presence of tumor necrosis factor (TNF)alpha. MMP-9 mRNA, protein levels and pro-MMP-9 activity were determined using real-time polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA) and zymogram assays. Pretreatment of frass with aprotinin abolished protease activity. PD98059, a chemical inhibitor of extracellular signal regulated kinase (ERK), and SLIGKV, an activator of protease-activated receptor (PAR)-2 were also used. AP-1DNA binding was determined by electrophoretic mobility shift assay (EMSA) and ERK phosphorylation by Western blot analysis. RESULTS: Cockroach frass augmented TNFalpha-mediated MMP-9 mRNA and protein expression by a mechanism dependent on active serine proteases within frass and not on endogenous endotoxin. Frass increased ERK phosphorylation, and chemical inhibition of ERK attenuated cockroaches' effects on MMP-9. Serine proteases are known to activate the PAR-2 receptor. We found that selective activation of PAR-2 using the peptide SLIGKV augmented TNFalpha-induced MMP-9 protein levels and increased ERK phosphorylation. Frass and SLIGKV each increased AP-1 translocation and DNA binding. CONCLUSIONS: These data suggest that German cockroach frass contains active serine proteases which augment TNFalpha-induced MMP-9 expression by a mechanism involving PAR-2, ERK and AP-1.
机译：背景：基质金属蛋白酶（MMP）消化细胞外基质蛋白，并可能在支气管哮喘的发病机理中起作用。与对照组相比，哮喘患者支气管肺泡灌洗液和痰中MMP-9水平升高。由于暴露于蟑螂是哮喘的环境危险因素，因此我们试图研究德国蟑螂粪便残留物（frass）对MMP-9表达的作用。方法：在不存在或存在肿瘤坏死因子（TNF）α的情况下，用蟑螂法治疗人支气管上皮细胞（16HBE140-）和原代正常人支气管上皮细胞。使用实时聚合酶链反应（PCR），酶联免疫吸附测定（ELISA）和酶谱测定法测定MMP-9 mRNA，蛋白水平和前MMP-9活性。用抑肽酶预处理油菜消除了蛋白酶的活性。还使用了PD98059（一种细胞外信号调节激酶（ERK）的化学抑制剂）和SLIGKV（一种蛋白酶激活的受体（PAR）-2的激活剂）。 AP-1DNA结合通过电泳迁移率测定（EMSA）和ERK磷酸化通过Western blot分析来确定。结果：蟑螂通过依赖于雀斑内活性丝氨酸蛋白酶而非内源性内毒素的机制来增强TNFalpha介导的MMP-9 mRNA和蛋白表达。 Frass增加了ERK的磷酸化，并且对ERK的化学抑制减弱了蟑螂对MMP-9的作用。已知丝氨酸蛋白酶可激活PAR-2受体。我们发现使用肽SLIGKV选择性激活PAR-2可增加TNFalpha诱导的MMP-9蛋白水平并增加ERK磷酸化。 Frass和SLIGKV各自增加AP-1易位和DNA结合。结论：这些数据表明德国蟑螂雀斑含有活性丝氨酸蛋白酶，通过涉及PAR-2，ERK和AP-1的机制增强TNFalpha诱导的MMP-9表达。

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