Hyaluronidase expression and activity is regulated by pro-inflammatory cytokines in human airway epithelial cells.
Hyaluronidase expression and activity is regulated by pro-inflammatory cytokines in human airway epithelial cells.
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DOI：
10.1165/rcmb.2007-0361oc
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发表时间：
2008-04
影响因子：
6.4
通讯作者：
María Elena Monzó;D. Manzanares;N. Schmid;S. Marina Casalino-Matsuda;R. Forteza;Monzó N
中科院分区：
文献类型：
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作者：
María Elena Monzó;D. Manzanares;N. Schmid;S. Marina Casalino-Matsuda;R. Forteza;Monzó N
透明质酸（HA）作为高分子量聚合物存在于气道上皮的顶端表面。由于HA解聚引发了一系列事件，导致激肽的产生和生长因子的加工，在本工作中，我们使用原代培养的人支气管上皮（HBE）细胞生长在空气-液体界面（ALI），以评估透明质酸酶（Hyal）的活性HA酶谱，基因表达的定量实时PCR，并通过共聚焦显微镜定位。由于TNF-α和IL-1 β在其他细胞中诱导Hyals，我们测试了它们对Hyals表达和活性的影响。我们发现Hyal样活性存在于HBE细胞的顶端和基底侧分泌物中，其中Hyals 1，2和3被表达，并且IL-1 β与TNF-α协同作用以增加基因表达和活性。共聚焦显微镜显示Hyal 1、2和3定位于细胞内，而Hyal 2也在与质膜相关的顶端极处表达，并且在顶端分泌物上以可溶性形式表达。正常个体和哮喘个体的组织切片显示Hyal分布模式分别与未处理的HBE细胞或暴露于细胞因子的细胞上观察到的模式相似。此外，与正常肺供体和健康志愿者相比，在哮喘受试者的气管切片和支气管肺泡灌洗（BAL）中观察到表达和活性增加。我们的观察表明Hyal 1、2和3在气道上皮细胞中表达，并且可能以协调的方式在与TNF-α和IL-1 β上调相关的炎症过程中（如过敏原诱导的哮喘反应）发挥作用，以降低HA水平。
Hyaluronan (HA) is present at the apical surface of airway epithelium as a high-molecular-weight polymer. Since HA depolymerization initiates a cascade of events that results in kinin generation and growth factor processing, in the present work we used primary cultures of human bronchial epithelial (HBE) cells grown at the air-liquid interface (ALI) to assess hyaluronidase (Hyal) activity by HA zymography, gene expression by quantitative real-time PCR, and localization by confocal microscopy. Because TNF-alpha and IL-1beta induce Hyals in other cells, we tested their effects on Hyals expression and activity. We found that Hyal-like activity is present in the apical and basolateral secretions from HBE cells where Hyals 1, 2, and 3 are expressed, and that IL-1beta acts synergistically with TNF-alpha to increase gene expression and activity. Confocal microscopy showed that Hyals 1, 2, and 3 were localized intracellularly, while Hyal2 was also expressed at the apical pole associated with the plasma membrane, and in a soluble form on the apical secretions. Tissue sections from normal individuals and from individuals with asthma showed a Hyal distribution pattern similar to that observed on nontreated HBE cells or exposed to cytokines, respectively. In addition, increased expression and activity were observed in tracheal sections and in bronchoalveolar lavage (BAL) obtained from subjects with asthma when compared with normal lung donors and healthy volunteers. Our observations indicate that Hyal 1, 2, and 3 are expressed in airway epithelium and may operate in a coordinated fashion to depolymerize HA during inflammation associated with up-regulation of TNF-alpha and IL-1beta, such as allergen-induced asthmatic responses.