Tai Emily K K, Wong Helen P S, Lam Emily K Y, Wu William K K, Yu L, Koo Marcel W L, Cho C H
Department of Pharmacology, The University of Hong Kong, Hong Kong, China.
J Cell Biochem. 2008 May 1;104(1):251-8. doi: 10.1002/jcb.21615.
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 microg/ml) and significantly stimulated mucus synthesis by increasing the D-[6-(3)H] 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.
黏液在胃肠道形成物理屏障。它在预防黏膜损伤和炎症方面发挥着重要作用。我们的动物研究表明，抗菌肽“cathelicidin”可增加黏液厚度并预防结肠炎症。在本研究中，我们检测了该肽在人结肠细胞系（HT - 29）中增加黏液合成的直接作用及其机制。人cathelicidin（LL - 37）呈剂量依赖性（10 - 40微克/毫升）显著刺激黏液合成，通过增加细胞中D - [6 - （3）H]氨基葡萄糖的掺入量。实时PCR数据显示，添加LL - 37可使MUC1和MUC2 mRNA水平增加超过50%。用MUC1和MUC2 siRNAs处理可使LL - 37对黏液合成的刺激作用恢复正常。LL - 37还可激活细胞中丝裂原活化蛋白（MAP）激酶的磷酸化。MAP激酶途径的特异性抑制剂U0126可完全阻断LL - 37诱导的MUC1和MUC2表达增加以及黏液合成。综上所述，LL - 37可通过激活人结肠细胞中MUC1和MUC2的表达以及MAP激酶途径直接刺激黏液合成。
