Topical Dexamethasone Administration Impairs Protein Synthesis and Neuronal Regeneration in the Olfactory Epithelium.
Topical Dexamethasone Administration Impairs Protein Synthesis and Neuronal Regeneration in the Olfactory Epithelium.
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DOI：
10.3389/fnmol.2018.00050
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发表时间：
2018
影响因子：
4.8
通讯作者：
Glezer I
中科院分区：
文献类型：
--
作者：
Crisafulli U;Xavier AM;Dos Santos FB;Cambiaghi TD;Chang SY;Porcionatto M;Castilho BA;Malnic B;Glezer I
鼻黏膜的慢性炎症过程与嗅觉差有关。嗅觉上皮（OE）免疫细胞的过度激活通常与嗅觉功能丧失有关，局部类固醇抗炎药已被广泛用于治疗这种情况。这种治疗策略是否能直接影响OE的再生过程尚不清楚。在这项研究中，我们发现鼻腔局部应用地塞米松（DEX； 200或800 ng/鼻孔），一种强效的合成抗炎类固醇，可以减轻由革兰氏阴性菌脂多糖（LPS）鼻内灌注引起的OE病变。相比之下，病变建立后反复局部应用DEX （400 ng/鼻孔）限制了LPS或甲巯咪唑促进损伤后嗅觉感觉神经元的再生。值得注意的是，当药物连续3天输注时，观察到DEX效应。消炎药不诱导OE祖细胞死亡，但在治疗过程中观察到哺乳动物雷帕霉素下游信号通路靶点的紊乱和蛋白质合成的损害。此外，在没有炎症环境下对OE神经球进行的体外研究表明，糖皮质激素受体的参与直接减少了OE祖细胞的增殖。我们的研究结果表明，DEX可以干扰OE的内在再生细胞机制，引起人们对局部使用抗炎类固醇作为进行性嗅觉功能损伤的危险因素的关注。
Chronic inflammatory process in the nasal mucosa is correlated with poor smell perception. Over-activation of immune cells in the olfactory epithelium (OE) is generally associated with loss of olfactory function, and topical steroidal anti-inflammatory drugs have been largely used for treating such condition. Whether this therapeutic strategy could directly affect the regenerative process in the OE remains unclear. In this study, we show that nasal topical application of dexamethasone (DEX; 200 or 800 ng/nostril), a potent synthetic anti-inflammatory steroid, attenuates OE lesion caused by Gram-negative bacteria lipopolysaccharide (LPS) intranasal infusion. In contrast, repeated DEX (400 ng/nostril) local application after lesion establishment limited the regeneration of olfactory sensory neurons after injury promoted by LPS or methimazole. Remarkably, DEX effects were observed when the drug was infused as 3 consecutive days regimen. The anti-inflammatory drug does not induce OE progenitor cell death, however, disturbance in mammalian target of rapamycin downstream signaling pathway and impairment of protein synthesis were observed during the course of DEX treatment. In addition, in vitro studies conducted with OE neurospheres in the absence of an inflammatory environment showed that glucocorticoid receptor engagement directly reduces OE progenitor cells proliferation. Our results suggest that DEX can interfere with the intrinsic regenerative cellular mechanisms of the OE, raising concerns on the use of topical anti-inflammatory steroids as a risk factor for progressive olfactory function impairment.
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影响因子：
5.3
作者：
Goldstein, Evan Z.;Church, Jamie S.;McTigue, Dana M.
通讯作者：
McTigue, Dana M.
影响因子：
3.3
作者：
De Bosscher, K;Vanden Berghe, W;Haegeman, G
通讯作者：
Haegeman, G
影响因子：
6.1
作者：
Bergman, U;Östergren, A;Brittebo, EB
通讯作者：
Brittebo, EB
影响因子：
4.8
作者：
Glezer, Isaias;Lapointe, Amelie;Rivest, Serge
通讯作者：
Rivest, Serge
DOI：
10.1073/pnas.1620664114
发表时间：
2017-07-25
影响因子：
11.1
作者：
Chen, Mengfei;Reed, Randall R.;Lane, Andrew P.
通讯作者：
Lane, Andrew P.