Function and regulation of SPLUNC1 protein in mycoplasma infection and allergic inflammation
Function and regulation of SPLUNC1 protein in mycoplasma infection and allergic inflammation
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DOI：
10.4049/jimmunol.179.6.3995
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发表时间：
2007-09-15
影响因子：
4.4
通讯作者：
Martin, Richard J.
中科院分区：
文献类型：
--
作者：
Chu, Hong Wei;Thaikoottathil, Jyoti;Martin, Richard J.
呼吸道感染，包括肺炎支原体（MP），有助于哮喘的病理生物学。迄今为止，哮喘患者对气道MP感染易感性增加的机制仍不清楚。短腭、肺和鼻上皮克隆1（SPLUNC 1）蛋白是最近描述的一种大气道上皮细胞衍生分子，被预测发挥宿主防御活性。然而，SPLUNC 1在感染性或过敏性环境中的功能和调节仍然是未知的。我们确定了Mp感染中SPLUNC 1蛋白的宿主防御和抗炎功能以及Mp和过敏性炎症对SPLUNC 1的调节（例如，IL-13）。通过使用SPLUNC 1重组蛋白、过表达和RNA干扰在Mp或人气道上皮细胞培养物中检测SPLUNC 1功能。人和小鼠支气管上皮细胞SPLUNC 1进行了检查，使用免疫染色，蛋白质印迹，ELISA，激光捕获显微切割，和实时PCR。使用Mp感染和过敏性炎症的小鼠模型以及正常人原代支气管上皮细胞的气-液界面培养物来研究Mp和IL-13对SPLUNC 1的调节。我们发现：1）SPLUNC 1蛋白降低MP水平并抑制由MP衍生脂蛋白诱导的上皮IL-8产生; 2）正常人和小鼠大气道上皮细胞表达高水平的SPLUNC 1;和3）尽管MP感染增加SPLUNC 1，但IL-13显著降低SPLUNC 1表达和MP清除。我们的研究结果表明，SPLUNC 1作为一种新的宿主防御蛋白对MP和过敏性环境显着降低SPLUNC 1的表达，这可能部分有助于过敏性气道细菌感染的持续性。
Respiratory infections, including Mycoplasma pneumoniae (Mp), contribute to asthma pathobiology. To date, the mechanisms underlying the increased susceptibility of asthmatics to airway Mp infection remain unclear. Short palate, lung, and nasal epithelium clone 1 (SPLUNC1) protein is a recently described large airway epithelial cell-derived molecule that was predicted to exert host defense activities. However, SPLUNC1 function and regulation in an infectious or allergic milieu are still unknown. We determined host defense and anti-inflammatory functions of SPLUNC1 protein in Mp infection and the regulation of SPLUNC1 by Mp and allergic inflammation (e.g., IL-13). SPLUNC1 function was examined in Mp or human airway epithelial cell cultures by using SPLUNC1 recombinant protein, overexpression and RNA interference. Human and mouse bronchial epithelial SPLUNC1 was examined using immunostaining, Western blotting, ELISA, laser capture microdissection, and real-time PCR. Mouse models of Mp infection and allergic inflammation and air-liquid interface cultures of normal human primary bronchial epithelial cells were used to study SPLUNC1 regulation by Mp and IL-13. We found that: 1) SPLUNC1 protein decreased Mp levels and inhibited epithelial IL-8 production induced by Mp-derived lipoproteins; 2) normal human and mouse large airway epithelial cells expressed high levels of SPLUNC1; and 3) although Mp infection increased SPLUNC1, IL-13 significantly decreased SPLUNC1 expression and Mp clearance. Our results suggest that SPLUNC1 serves as a novel host defense protein against Mp and that an allergic setting markedly reduces SPLUNC1 expression, which may in part contribute to the persistent nature of bacterial infections in allergic airways.