Dexamethasone inhibits repair of human airway epithelial cells mediated by glucocorticoid-induced leucine zipper (GILZ).
Dexamethasone inhibits repair of human airway epithelial cells mediated by glucocorticoid-induced leucine zipper (GILZ).
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DOI：
10.1371/journal.pone.0060705
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Fu Z
中科院分区：
文献类型：
--
作者：
Liu J;Zhang M;Niu C;Luo Z;Dai J;Wang L;Liu E;Fu Z
糖皮质激素(GCs)是治疗哮喘的一线药物，具有抗炎作用，但也会阻碍呼吸道上皮损伤的修复。据报道，抗炎蛋白GC诱导的亮氨酸拉链(GILZ)可以抑制丝裂原活化蛋白激酶(MAPK)-细胞外信号调节激酶(ERK)信号通路的激活，从而促进受损区域周围呼吸道上皮细胞的修复。我们研究了GC地塞米松(DEX)对气道上皮修复的抑制作用是否由GILZ介导。采用RT-PCR和Western印迹方法检测地塞米松对人呼吸道上皮细胞GILZ mRNA和GILZ蛋白表达及MAPK-ERK信号转导通路的影响。我们通过小干扰RNA、四甲基偶氮唑蓝、CFSE标记、伤口愈合和细胞迁移分析，进一步评价了GILZ在介导地塞米松对MAPK-ERK信号通路和呼吸道上皮修复的影响中的作用。地塞米松可增加人呼吸道上皮细胞系的GILZ mRNA和GILZ蛋白水平。此外，地塞米松还抑制MAPK-ERK信号通路中Raf-1、MEK1/2、ERK1/2的磷酸化，抑制细胞的增殖和迁移。然而，当GILZ基因沉默时，DEX在细胞中的抑制作用减弱。地塞米松抑制上皮损伤修复的部分机制是通过激活GILZ来抑制MAPK-ERK信号通路的激活、增殖和迁移。我们的研究表明DEX参与了这一过程，并加深了我们对GCs双重角色的理解。
Glucocorticoids (GCs) are a first-line treatment for asthma for their anti-inflammatory effects, but they also hinder the repair of airway epithelial injury. The anti-inflammatory protein GC-induced leucine zipper (GILZ) is reported to inhibit the activation of the mitogen-activated protein kinase (MAPK)-extracellular-signal-regulated kinase (ERK) signaling pathway, which promotes the repair of airway epithelial cells around the damaged areas. We investigated whether the inhibition of airway epithelial repair imposed by the GC dexamethasone (DEX) is mediated by GILZ. We tested the effect of DEX on the expressions of GILZ mRNA and GILZ protein and the MAPK-ERK signaling pathway in human airway epithelial cells, via RT-PCR and Western blot. We further evaluated the role of GILZ in mediating the effect of DEX on the MAPK-ERK signaling pathway and in airway epithelium repair by utilizing small-interfering RNAs, MTT, CFSE labeling, wound-healing and cell migration assays. DEX increased GILZ mRNA and GILZ protein levels in a human airway epithelial cell line. Furthermore, DEX inhibited the phosphorylation of Raf-1, Mek1/2, Erk1/2 (components of the MAPK-ERK signaling pathway), proliferation and migration. However, the inhibitory effect of DEX was mitigated in cells when the GILZ gene was silenced. The inhibition of epithelial injury repair by DEX is mediated in part by activation of GILZ, which suppressed activation of the MAPK-ERK signaling pathway, proliferation and migration. Our study implicates the involvement of DEX in this process, and furthers our understanding of the dual role of GCs.
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影响因子：
4.3
作者：
Tam, Anthony;Wadsworth, Samuel;Sin, Don D
通讯作者：
Sin, Don D
影响因子：
3.7
作者：
Köberle M;Göppel D;Grandl T;Gaentzsch P;Manncke B;Berchtold S;Müller S;Lüscher B;Asselin-Labat ML;Pallardy M;Sorg I;Langer S;Barth H;Zumbihl R;Autenrieth IB;Bohn E
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Bohn E
影响因子：
15.9
作者：
Ayroldi, Emira;Zollo, Ornella;Riccardi, Carlo
通讯作者：
Riccardi, Carlo
DOI：
10.1152/ajplung.00322.2005
发表时间：
2006-10-01
影响因子：
4.9
作者：
Dorscheid, Delbert R.;Patchell, Benjamin J.;White, Steven R.
通讯作者：
White, Steven R.
影响因子：
14.2
作者：
Eddleston, Jane;Herschbach, Jack;Zuraw, Bruce L.
通讯作者：
Zuraw, Bruce L.