Effects of matrix metalloproteinase inhibitor on LPS-induced goblet cell metaplasia
Effects of matrix metalloproteinase inhibitor on LPS-induced goblet cell metaplasia
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DOI：
10.1152/ajplung.00047.2003
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发表时间：
2004-07-01
影响因子：
4.9
通讯作者：
Yoo, SH
中科院分区：
文献类型：
--
作者：
Kim, JH;Lee, SY;Yoo, SH
众所周知，肺部细菌感染会引起炎症反应，从而导致粘液过度分泌。此外，据报道，中性粒细胞炎症诱导的表皮生长因子受体(EGFR)的表达和激活调节了呼吸道粘蛋白的合成。此外，基质金属蛋白酶(MMPs)，特别是基质金属蛋白酶-9，已被报道促进激活的中性粒细胞的迁移。本研究探讨脂多糖诱导的杯状细胞化生与EGFR表达的关系及基质金属蛋白酶抑制剂(MMPI)的作用。将不同浓度的内毒素注入无病原体SD大鼠的气管内，观察不同时间内毒素对大鼠呼吸道的影响。为了研究基质金属蛋白酶-9的作用，我们在注射脂多糖前3天和之后每天给予MMPI治疗。中性粒细胞浸润、阿尔新蓝/高碘酸席夫(AB/PAS)染色和免疫组织化学染色检测MUC5AC、EGFR和MMP9的表达。内毒素以时间和剂量依赖的方式增加AB/PAS和MUC5AC染色，MMPI处理可显著抑制GC的化生。气管内注射脂多糖还可诱导气道上皮细胞中性粒细胞的浸润和EGFR、MMP9的表达，MMPI可显著抑制中性粒细胞募集、GC化生、EGFR和MMP9的表达。这项研究表明，基质金属蛋白酶-9和EGFR级联反应与内毒素诱导的粘液高分泌有关。
Bacterial infections of the lung are known to induce inflammatory responses, which lead to mucus hypersecretion. Moreover, mucin synthesis in the airways has been reported to be regulated by neutrophilic inflammation-induced epidermal growth factor receptor (EGFR) expression and its activation. Furthermore, matrix metalloproteinases (MMPs), especially MMP-9, have been reported to promote the transmigration of activated neutrophils. In this study, we investigated the associations between lipopolysaccharide (LPS)-induced goblet cell (GC) metaplasia and EGFR expression and the effects of MMP inhibitor (MMPI). Various concentrations of LPS were instilled into the tracheas of pathogen-free Sprague-Dawley rats, and airways were examined at different times after LPS instillation. To examine the role of MMP-9, we treated rats 3 days before LPS instillation and daily thereafter with MMPI. Neutrophilic infiltration, Alcian blue/periodic acid-Schiff (AB/PAS) staining, and immunohistochemical staining for MUC5AC, EGFR, and MMP-9 were performed. The instillation of LPS increased AB/PAS and MUC5AC staining in time-and dose-dependent manners, and treatment with MMPI significantly prevented GC metaplasia. The instillation of LPS into the trachea also induced neutrophilic infiltration and EGFR and MMP-9 expression in the airway epithelium, and MMPI was found to significantly prevent neutrophil recruitment, GC metaplasia, and EGFR and MMP-9 expression. This study demonstrates that the MMP-9 and EGFR cascades are associated with LPS-induced mucus hypersecretion.