Cathelicidin stimulates colonic mucus synthesis by up‐regulating MUC1 and MUC2 expression through a mitogen‐activated protein kinase pathway
Cathelicidin stimulates colonic mucus synthesis by up‐regulating MUC1 and MUC2 expression through a mitogen‐activated protein kinase pathway
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DOI：
10.1002/jcb.21615
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发表时间：
2008-05
影响因子：
4
通讯作者：
E. K. Tai;H. Wong;Emily Y M Lam;W. Wu;L. Yu;M. Koo;C. Cho
中科院分区：
文献类型：
--
作者：
E. K. Tai;H. Wong;Emily Y M Lam;W. Wu;L. Yu;M. Koo;C. Cho
粘液形成胃肠道的物理屏障。它对于预防粘膜损伤和炎症起着重要作用。我们的动物研究表明，抗菌肽“cathelicidin”可增加粘液厚度并预防结肠炎症。在当前的研究中，我们研究了该肽增加人类结肠细胞系（HT-29）中粘液合成的直接作用和机制。人导管素 (LL-37) 呈剂量依赖性（10-40 µg/ml），通过增加细胞中 D-[6-3H] 葡萄糖胺的掺入显着刺激粘液合成。实时 PCR 数据显示，添加 LL-37 导致 MUC1 和 MUC2 mRNA 水平增加超过 50%。 MUC1 和 MUC2 siRNA 治疗使 LL-37 对粘液合成的刺激作用正常化。 LL-37 还激活细胞中丝裂原激活蛋白 (MAP) 激酶的磷酸化。 MAP 激酶途径的特异性抑制剂 U0126 完全阻断了 LL-37 引起的 MUC1 和 MUC2 表达的增加以及粘液合成。综上所述，LL-37 可以通过激活人结肠细胞中的 MUC1 和 MUC2 表达以及 MAP 激酶通路来直接刺激粘液合成。 J.细胞。生物化学。 104: 251–258, 2008。© 2007 Wiley-Liss, Inc.
Mucus forms the physical barrier along the gastrointestinal tract. It plays an important role to prevent mucosal damage and inflammation. Our animal study showed that antibacterial peptide ‘cathelicidin’ increased mucus thickness and prevented inflammation in the colon. In the current study, we examined the direct effect and mechanisms by which the peptide increased mucus synthesis in a human colonic cell line (HT‐29). Human cathelicidin (LL‐37) dose‐dependently (10–40 µg/ml) and significantly stimulated mucus synthesis by increasing the D‐[6‐3H] glucosamine incorporation in the cells. Real‐time PCR data showed that addition of LL‐37 induced more than 50% increase in MUC1 and MUC2 mRNA levels. Treatment with MUC1 and MUC2 siRNAs normalized the stimulatory action of LL‐37 on mucus synthesis. LL‐37 also activated the phosphorylation of mitogen‐activated protein (MAP) kinase in the cells. A specific inhibitor of the MAP kinase pathway, U0126, completely blocked the increase of MUC1 and MUC2 expression as well as mucus synthesis by LL‐37. Taken together, LL‐37 can directly stimulate mucus synthesis through activation of MUC1 and MUC2 expression and MAP kinase pathway in human colonic cells. J. Cell. Biochem. 104: 251–258, 2008. © 2007 Wiley‐Liss, Inc.