WFDC2 (HE4): a potential role in the innate immunity of the oral cavity and respiratory tract and the development of adenocarcinomas of the lung.
WFDC2 (HE4): a potential role in the innate immunity of the oral cavity and respiratory tract and the development of adenocarcinomas of the lung.
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DOI：
10.1186/1465-9921-7-61
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发表时间：
2006-04-06
影响因子：
5.8
通讯作者：
Bingle CD
中科院分区：
文献类型：
--
作者：
Bingle L;Cross SS;High AS;Wallace WA;Rassl D;Yuan G;Hellstrom I;Campos MA;Bingle CD
乳清酸性蛋白结构域是一个进化保守的基序，在许多蛋白质中发现，其中研究最好的是参与多个上皮细胞天然免疫防御的抗蛋白酶。我们最近对WFDC2基因进行了鉴定，该基因编码一个含有两个WAP结构域的蛋白，最初被认为是附睾症的标志，并表明它在肺和唾液腺中高度表达。WFDC2蛋白在这些位点的确切位置还没有被描述。我们使用免疫组织化学方法对WFDC2在呼吸道、鼻咽和口咽的正常组织中的定位，以及在囊性纤维化和一系列肺癌的慢性炎症肺中的定位。我们通过对原代培养的人肺细胞进行WFDC2基因表达的分子分析来补充这些研究。WFDC2在上呼吸道的一些上皮细胞以及粘膜下腺的粘液细胞和导管中表达。外周肺未见染色。在主要的唾液腺、鼻、鼻窦、舌后和扁桃体的小腺中可以发现强烈的染色。对相关蛋白分泌性白细胞蛋白抑制物(SLPI)的研究表明，虽然这两种蛋白在相似的组织中表达，但精确的细胞定位不同。囊性纤维化患者WFDC2的表达和定位显著增加。在相同的样本中，SLPI的表达大大降低。在培养的气管-支气管上皮细胞中，WFDC2和SLPI的表达在分化过程中受到不同的调节，但WFDC2不受促炎介质的诱导。大多数腺癌用WFDC2染色，而极少数鳞癌、小细胞癌和大细胞癌显示局灶性染色。这与肿瘤分级没有明显的关联。我们认为，这些研究支持WFDC2可能是肺、鼻和口腔固有免疫防御的组成部分的假设，并表明WFDC2与相关的包含WAP结构域的蛋白在上皮性宿主防御中起协同作用。我们还建议，WFDC2在肺癌中的重新表达可能被证明与肿瘤类型有关，应该进行进一步的详细研究。
The Whey Acidic Protein domain is an evolutionarily conserved motif found in a number of proteins, the best studied of which are antiproteinases involved in the innate immune defence of multiple epithelia. We recently characterised the WFDC2 gene which encodes a two WAP domain-containing protein, initially suggested as a marker for epididymis, and showed that it is highly expressed in the lung and salivary gland. The precise location of WFDC2 protein in these sites has not been described. We used immunohistochemistry to localise WFDC2 in normal tissues of the respiratory tract, naso- and oropharynx, as well as in chronically inflamed lung from Cystic Fibrosis and a range of pulmonary carcinomas. We have complemented these studies with molecular analysis of WFDC2 gene expression in primary human lung cell cultures. WFDC2 is expressed in some epithelial cells of the upper airways as well as in mucous cells and ducts of submucosal glands. No staining was seen in peripheral lung. Intense staining is found in major salivary glands and in minor glands of the nose, sinuses, posterior tongue and tonsil. Studies with the related protein Secretory Leukocyte Protease Inhibitor (SLPI) show that although both proteins are expressed in similar tissues, the precise cellular localisation differs. Significant increases in expression and localisation of WFDC2 are seen in patients with Cystic Fibrosis. SLPI expression was greatly reduced in the same samples. In cultures of tracheobronchial epithelial cells, expression of WFDC2 and SLPI are differentially regulated during differentiation yet WFDC2 is not induced by pro-inflammatory mediators. The majority of adenocarcinomas stain with WFDC2 whilst a significant minority of squamous, small cell and large cell carcinomas exhibit focal staining. There is no clear association with tumour grade. We believe that these studies support the hypothesis that WFDC2 may be a component of the innate immune defences of the lung, nasal and oral cavities and suggest that WFDC2 functions in concert with related WAP domain containing proteins in epithelial host defence. We also suggest that WFDC2 re-expression in lung carcinomas may prove to be associated with tumour type and should be studied in further detail.
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影响因子：
3.1
作者：
Hiemstra, PS;Maassen, RJ;Dijkman, JH
通讯作者：
Dijkman, JH
影响因子：
45.3
作者：
Endoh, H;Tomida, S;Mitsudomi, T
通讯作者：
Mitsudomi, T
影响因子：
7.3
作者：
Bingle, L;Cross, SS;Bingle, CD
通讯作者：
Bingle, CD
影响因子：
3.1
作者：
Ding, A;Thieblemont, N;Wright, S
通讯作者：
Wright, S
DOI：
10.1016/s0167-4781(00)00196-2
发表时间：
2000-10-02
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION
影响因子：
--
作者：
Bingle, CD;Bingle, L
通讯作者：
Bingle, L