Lipopolysaccharide disrupts the milk-blood barrier by modulating claudins in mammary alveolar tight junctions.
Lipopolysaccharide disrupts the milk-blood barrier by modulating claudins in mammary alveolar tight junctions.
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DOI：
10.1371/journal.pone.0062187
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Kumura H
中科院分区：
文献类型：
--
作者：
Kobayashi K;Oyama S;Numata A;Rahman MM;Kumura H
乳腺炎，即乳腺的炎症，是乳制品行业中最昂贵的常见疾病，并且是由包括大肠杆菌在内的乳腺病原菌引起的。细菌侵入乳腺肺泡腔并破坏血乳屏障。在正常乳腺中，肺泡上皮紧密连接（TJ）通过阻断乳汁成分从腔侧渗漏到血清中来贡献肺泡上皮的血乳屏障。在这项研究中，我们专注于参与肺泡上皮TJ的claudin亚型，因为claudin的组成是影响TJ渗透性的重要因素。在正常小鼠泌乳乳腺中，肺泡TJ由claudin-3组成，而没有claudin-1、-4和-7。在脂多糖（LPS）诱导的乳腺炎，肺泡TJ表现出2阶段的组成变化的claudins。首先，在封闭蛋白-3的质的变化，推测引起的磷酸化和参与封闭蛋白-7在肺泡TJs，被认为是平行的荧光素异硫氰酸酯结合的白蛋白（FITC-白蛋白）通过肺泡上皮细胞的泄漏。第二，在LPS注射后12 h，claudin-4与claudin-3和claudin-7一起参与肺泡TJ。免疫组化染色也观察到claudin-1的部分定位。与肺泡TJs的第二次变化相一致，通过β-酪蛋白的异位定位和大量FITC-白蛋白的渗漏来识别血-乳屏障的严重破坏。LPS刺激后，肺泡上皮细胞Toll样受体4（TLR 4）定位于腔侧，NFκB B活化。我们认为，削弱和破坏的血乳屏障所造成的组成变化的封闭蛋白在肺泡上皮TJ通过LPS/TLR 4信号。
Mastitis, inflammation of the mammary gland, is the most costly common disease in the dairy industry, and is caused by mammary pathogenic bacteria, including Escherichia coli. The bacteria invade the mammary alveolar lumen and disrupt the blood-milk barrier. In normal mammary gland, alveolar epithelial tight junctions (TJs) contribute the blood-milk barrier of alveolar epithelium by blocking the leakage of milk components from the luminal side into the blood serum. In this study, we focused on claudin subtypes that participate in the alveolar epithelial TJs, because the composition of claudins is an important factor that affects TJ permeability. In normal mouse lactating mammary glands, alveolar TJs consist of claudin-3 without claudin-1, -4, and -7. In lipopolysaccharide (LPS)-induced mastitis, alveolar TJs showed 2-staged compositional changes in claudins. First, a qualitative change in claudin-3, presumably caused by phosphorylation and participation of claudin-7 in alveolar TJs, was recognized in parallel with the leakage of fluorescein isothiocyanate-conjugated albumin (FITC-albumin) via the alveolar epithelium. Second, claudin-4 participated in alveolar TJs with claudin-3 and claudin-7 12 h after LPS injection. The partial localization of claudin-1 was also observed by immunostaining. Coinciding with the second change of alveolar TJs, the severe disruption of the blood-milk barrier was recognized by ectopic localization of β-casein and much leakage of FITC-albumin. Furthermore, the localization of toll-like receptor 4 (TLR4) on the luminal side and NFκB activation by LPS was observed in the alveolar epithelial cells. We suggest that the weakening and disruption of the blood-milk barrier are caused by compositional changes of claudins in alveolar epithelial TJs through LPS/TLR4 signaling.
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DOI：
10.1083/jcb.201106011
发表时间：
2011-10-31
期刊：
The Journal of cell biology
影响因子：
--
作者：
Bonazzi M;Cossart P
通讯作者：
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影响因子：
2.1
作者：
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影响因子：
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DOI：
10.1023/b:jomg.0000017431.45314.07
发表时间：
2003-10-01
影响因子：
2.5
作者：
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通讯作者：
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人claudin-1、-3和-4中翻译后修饰的作用以及磷酸化和O-β-GlcNAc修饰之间的新串扰
影响因子：
2.8
作者：
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