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首页> 外文期刊>Journal of Allergy >Proteolytic Activity Present in House-Dust-Mite Extracts Degrades ENA-78/CXCL5 and Reduces Neutrophil Migration
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Proteolytic Activity Present in House-Dust-Mite Extracts Degrades ENA-78/CXCL5 and Reduces Neutrophil Migration

机译：屋尘螨提取物中存在的蛋白水解活性会降低ENA-78 / CXCL5并减少中性粒细胞迁移

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Background. Bronchial smooth muscle cells (BSMC) are a major source of proinflammatory and proangiogenic cytokines and chemokines, including VEGF and CXC-chemokines. CXC-chemokines act primarily on neutrophils, mediating their recruitment to and activation at the site of inflammation. In humans, house-dust mite (HDM) allergens can cause asthmatic exacerbations and trigger an inflammatory response through protease-dependent mechanisms. Objective. We investigated the effect HDM extract on the release of pro-angiogenic and proinflammatory cytokines from BSMC. Methods. Human primary BSMC were stimulated with HDM extract in the absence or presence of fetal calf serum (FCS). Twenty angiogenic cytokines were detected by a specific antibody array and modified protein levels were confirmed by ELISA. Neutrophil migration was measured using a 96-well Boyden chamber. Results. ENA-78/CXCL5 protein levels in conditioned medium of BSMC stimulated with HDM extract were significantly reduced (, ) but restored in the presence of 5% FCS. HDM extracts did not affect ENA-78/CXCL5 mRNA levels. Recombinant ENA-78/CXCL5 was degraded after incubation with HDM extracts (, ) but restored after the addition of the serine protease AEBSF. Neutrophil migration towards recombinant ENA-78/CXCL5 was also reduced in the presence of HDM extract. Conclusion. HDM proteases degrade ENA-78/CXCL5. Thus exposure to HDM allergens may alter ENA-78/CXCL5 levels in the lungs and may affect angiogenesis and the inflammatory response in the airways of asthma patients.
机译：背景。支气管平滑肌细胞（BSMC）是促炎和促血管生成细胞因子和趋化因子（包括VEGF和CXC趋化因子）的主要来源。 CXC趋化因子主要作用于中性粒细胞，介导其募集并在炎症部位活化。在人类中，屋尘螨（HDM）过敏原可导致哮喘加重，并通过蛋白酶依赖性机制触发炎症反应。目的。我们调查了HDM提取物对从BSMC释放促血管生成和促炎细胞因子的影响。方法。在胎牛血清（FCS）存在或不存在的情况下，用HDM提取物刺激人原代BSMC。通过特异性抗体阵列检测了二十种血管生成细胞因子，并通过ELISA证实了修饰的蛋白水平。中性粒细胞迁移使用96孔Boyden室进行测量。结果。 HDM提取物刺激的BSMC条件培养基中的ENA-78 / CXCL5蛋白水平显着降低（，），但在5％FCS的存在下恢复。 HDM提取物不影响ENA-78 / CXCL5 mRNA水平。与HDM提取物（，）孵育后，重组ENA-78 / CXCL5降解，但在添加丝氨酸蛋白酶AEBSF后恢复。在存在HDM提取物的情况下，嗜中性粒细胞向重组ENA-78 / CXCL5的迁移也减少了。结论。 HDM蛋白酶降解ENA-78 / CXCL5。因此，暴露于HDM过敏原可能会改变肺中的ENA-78 / CXCL5水平，并可能影响哮喘患者气道中的血管生成和炎症反应。

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