IL-6 and IL-8 increase the expression of glycosyltransferases and sulfotransferases involved in the biosynthesis of sialylated and/or sulfated Lewisx epitopes in the human bronchial mucosa
IL-6 and IL-8 increase the expression of glycosyltransferases and sulfotransferases involved in the biosynthesis of sialylated and/or sulfated Lewisx epitopes in the human bronchial mucosa
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DOI：
10.1042/bj20070958
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发表时间：
2008-02-15
影响因子：
4.1
通讯作者：
Delannoy, Philippe
中科院分区：
文献类型：
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作者：
Groux-Degroote, Sophie;Krzewinski-Recchi, Marie-Ange;Delannoy, Philippe
CF（囊性纤维化）患者的支气管粘蛋白显示糖基化改变，特别是唾液酸-刘易斯'（NeuAc α 2-3Gal β 1-4[Fuc α 1-3]GlcNAc-R）和6-磺基-唾液酸-刘易斯（x）（NeuAc α 2-3Gal β 1-4[Fuc α 1-3][SO 3 H-6]GlcNAc-R）末端结构的量增加。这些表位是铜绿假单胞菌的优先受体，铜绿假单胞菌是导致气道感染慢性化并参与CF患者发病和早期死亡的细菌。然而，这些糖基化变化不能直接与CFTR（CF跨膜传导调节因子）基因表达缺陷相关，因为分泌气道粘蛋白的细胞不表达或表达极少量的蛋白质。几项研究表明，炎症可能影响各种糖蛋白（包括粘蛋白）的糖基化和硫酸化。在本研究中，我们发现，用IL-6孵育肉眼可见的健康人支气管粘膜碎片，（白细胞介素-6）或IL-8导致1，3/4-岩藻糖基转移酶的表达显着增加[FUT 11 α 2-6-和α 2，3-唾液酸转移酶[ST 3GAL 6（α 2，3-唾液酸转移酶6基因）和ST 6 GAL 2（α 2，6-唾液酸转移酶2基因）]和GlcNAc-6-O-磺基转移酶[CHST 4（碳水化合物磺基转移酶4基因）和CHST 6] mRNA。同时，在高分子量蛋白质（包括MUC 4）的外周，唾液酸-刘易斯（x）和6-磺基-唾液酸-刘易斯（x）表位的量也增加了。总之，我们的研究结果表明，IL-6和-8可能有助于CF患者的人气道粘蛋白上唾液酸-刘易斯（x）和6-磺基-唾液酸-刘易斯（x）表位水平的增加。
Bronchial mucins from patients suffering from CF (cystic fibrosis) exhibit glycosylation alterations, especially increased amounts of the sialyl-Lewis' (NeuAc alpha 2-3Gal beta 1-4[Fuc alpha 1-3]GlcNAc-R) and 6-sulfo-sialyl-Lewis(x) (NeuAc alpha 2-3Gal beta 1-4[Fuc alpha 1-3][SO3H-6]GlcNAc-R) terminal structures. These epitopes are preferential receptors for Pseudomonas aeruginosa, the bacteria responsible for the chronicity of airway infection and involved in the morbidity and early death of CF patients. However, these glycosylation changes cannot be directly linked to defects in CFTR (CF transmembrane conductance regulator) gene expression since cells that secrete airway mucins express no or very low amounts of the protein. Several studies have shown that inflammation may affect glycosylation and sulfation of various glycoproteins, including mucins. In the present study, we show that incubation of macroscopically healthy fragments of human bronchial mucosa with IL-6 (interleukin-6) or IL-8 results in a significant increase in the expression of a 1,3/4-fucosyltransferases [FUT11 (fucosyltransferase 11 gene) and FUT3], alpha 2-6- and alpha 2,3-sialyltransferases [ST3GAL6 (alpha 2,3-sialyltransferase 6 gene) and ST6GAL2 (alpha 2,6-sialyltransferase 2 gene)] and GlcNAc-6-O-sulfotransferases [CHST4 (carbohydrate sulfotransferase 4 gene) and CHST6] mRNA. In parallel, the amounts of sialyl-Lewis(x) and 6-sulfo-sialyl-Lewis(x) epitopes at the periphery of high-molecular-mass proteins, including MUC4, were also increased. In conclusion, our results indicate that IL-6 and -8 may contribute to the increased levels of sialyl-Lewis(x) and 6-sulfo-sialyl-Lewis(x) epitopes on human airway mucins from patients with CF.