Expression and Roles of MMP-2, MMP-9, MMP-13, TIMP-1, and TIMP-2 in Allergic Nasal Mucosa.
Expression and Roles of MMP-2, MMP-9, MMP-13, TIMP-1, and TIMP-2 in Allergic Nasal Mucosa.
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DOI：
10.4168/aair.2012.4.4.231
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发表时间：
2012-07
期刊：
影响因子：
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通讯作者：
Okubo K
中科院分区：
文献类型：
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作者：
Mori S;Pawankar R;Ozu C;Nonaka M;Yagi T;Okubo K
变应性鼻炎（AR）和哮喘有许多共同的特征，但在AR中观察到的结构变化要少得多。基质金属蛋白酶（MMPs）是一类锌依赖性内肽酶家族，能够分解细胞外基质和基底膜，调节细胞浸润。我们分析了MMPs及其抑制剂，金属蛋白酶组织抑制剂（TIMPs）的表达，在过敏性鼻粘膜后鼻变应原攻击（NAC），并确定其与炎症细胞的关系。鼻粘膜标本是在对肥大的鼻甲进行手术时获得的。我们用屋尘螨（HDM）变应原盘和对照盘进行NAC，并在NAC后30分钟、6小时和12小时进行活检。对表达MMP-2、MMP-9、MMP-13、TIMP-1和TIMP-2的细胞以及嗜酸性粒细胞和肥大细胞进行化学分析。采用酶联免疫吸附法检测过敏性鼻粘膜中MMPs和TIMPs的含量。在NAC后30分钟，与对照粘膜相比，HDM暴露的鼻粘膜显示出显著更多的MMP-2+、MMP-9+、MMP-13+、TIMP-1+和TIMP-2+细胞，并且MMP-9+和TIMP-1+细胞的数量与肥大细胞的数量密切相关。NAC后6小时，MMP+和TIMP+细胞的数量在HDM暴露的粘膜和对照粘膜之间没有显著差异，但MMP+细胞与TIMP+细胞的比率在HDM暴露的粘膜中较高。在NAC后12小时，MMP-13+细胞的数量在HDM暴露的粘膜中倾向于更高，并且与嗜酸性粒细胞的数量密切相关。定量上，过敏性鼻粘膜中MMP-2、MMP-13的水平显著高于MMP-9的水平，TIMP-2的水平显著高于TIMP-1的水平。我们证实了过敏性鼻粘膜中MMP-2、MMP-9和MMP-13的表达增加，MMP与TIMP-1的比例较高，MMP-9与肥大细胞之间以及MMP-13与嗜酸性粒细胞之间存在强相关性。MMPs和TIMP之间的失衡可能有助于嗜酸性粒细胞和肥大细胞等炎症细胞向AR患者鼻粘膜迁移，表明MMPs在AR中可能发挥积极作用。
Allergic rhinitis (AR) and asthma share many characteristics, but structural changes are observed far less often in AR. Matrix metalloproteinases (MMPs) constitute a family of Zn-dependent endopeptidases that can decompose the extracellular matrix and basement membrane, and regulate cell infiltration. We analyzed the expression of MMPs and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs), in allergic nasal mucosa after nasal allergen challenge (NAC) and determined their relationship to inflammatory cells. Nasal mucosa specimens were obtained at surgery performed for hypertrophied turbinates. We performed NAC with house dust mite (HDM) allergen disks and control disks, and took biopsies at 30 minutes, 6 hours, and 12 hours after NAC. Cells expressing MMP-2, MMP-9, MMP-13, TIMP-1, and TIMP-2, as well as eosinophils and mast cells, were analyzed immunohistochemically. The MMPs and TIMPs in allergic nasal mucosa were quantified using enzyme-linked immunosorbent assays. At 30 minutes post-NAC, HDM-exposed nasal mucosa exhibited significantly more MMP-2+, MMP-9+, MMP-13+, TIMP-1+, and TIMP-2+ cells compared with control mucosa, and the numbers of MMP-9+ and TIMP-1+ cells correlated strongly with the number of mast cells. At 6 hours post-NAC, the numbers of MMP+ and TIMP+ cells did not differ significantly between HDM-exposed mucosa and control mucosa, but the ratios of MMP+ cells to TIMP+ cells were higher in HDM-exposed mucosa. At 12 hours post-NAC, the number of MMP-13+ cells tended to be higher in HDM-exposed mucosa and was strongly correlated with the number of eosinophils. Quantitatively, the levels of MMP-2 and MMP-13 were significantly higher than the MMP-9 level, and the TIMP-2 level was significantly higher than the TIMP-1 level in allergic nasal mucosa. We demonstrated increased expression of MMP-2, MMP-9, and MMP-13 in allergic nasal mucosa, high MMPs-to-TIMP-1 ratios, and a strong correlation between MMP-9 and mast cells and between MMP-13 and eosinophils. The imbalance between MMPs and TIMPs may contribute to the migration of inflammatory cells such as eosinophils and mast cells to the nasal mucosa of AR patients, suggesting a possible active role of MMPs in AR.