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地塞米松诱导新鲜分离的人鼻上皮细胞凋亡,同时阻断白细胞介素-8 的产生。

Dexamethasone-induced apoptosis of freshly isolated human nasal epithelial cells concomitant with abrogation of IL-8 production.

机构信息

Laboratory of Experimental Immunology, Catholic University Hospitals, Leuven, Belgium.

出版信息

Rhinology. 2010 Dec;48(4):401-7. doi: 10.4193/Rhino10.033.

Abstract

BACKGROUND

Human nasal epithelial cells (hNECs) are the first line of immune defense and are able to produce mediators that recruit, activate and prolong survival of immune cells, among which IL-8 takes an important place. Studies on IL-8 and effects of dexamethasone on hNECs have been hampered by methodological shortcomings. The purpose of the study is to investigate the contribution of freshly isolated hNECs to IL-8 production in chronic rhinosinusitis with nasal polyps (CRSwithNP). Secondly, the effects of dexamethasone treatment on hNEC apoptosis and IL-8 production are investigated.

METHODOLOGY

hNECs were freshly isolated from nasal polyp tissue and healthy inferior turbinate of NP patients (n=12) and from inferior turbinates of healthy donors (n=19) by protease treatment and two negative selection procedures. hNECs were incubated with IL-1β (10ng/ml), TNFα (10ng/ml) or dexamethasone (10, 100 and 1000 Amicrog/ml). After 24h, IL-8 levels were determined in the supernatants by ELISA. Finally, hNECs were incubated with increasing doses of dexamethasone and stained with trypan-blue and annexin-FITC/PI to study apoptosis.

RESULTS

hNECs isolated from nasal turbinates of healthy and NP patients and polyp tissue from NP patients produced similar levels of IL-8. IL-1β induced higher levels of IL-8 production in all types of hNECs without differences between control and NP tissue. Dexamethasone induced apoptosis of hNECs concomitant with abrogation of IL-8 production by hNECs.

CONCLUSIONS

IL-8 production by human nasal epithelial cells does not differ between NP and healthy tissue under baseline nor stimulatory conditions. Dexamethasone induces apoptosis of hNECs and abrogates IL-8 production.

摘要

背景

人鼻腔上皮细胞(hNEC)是第一道免疫防线,能够产生招募、激活并延长免疫细胞存活的介质,其中 IL-8 起着重要作用。由于方法学上的缺陷,IL-8 及地塞米松对 hNEC 的作用的研究受到了阻碍。本研究旨在探讨新鲜分离的 hNEC 在伴有鼻息肉的慢性鼻-鼻窦炎(CRSwNP)中产生 IL-8 的作用。其次,研究地塞米松处理对 hNEC 凋亡和 IL-8 产生的影响。

方法

蛋白酶处理和两次阴性选择程序从 NP 患者的鼻息肉组织和下鼻甲(n=12)以及健康供体的下鼻甲(n=19)中新鲜分离 hNEC。将 hNEC 与 IL-1β(10ng/ml)、TNFα(10ng/ml)或地塞米松(10、100 和 1000Amicrog/ml)孵育。24 小时后,通过 ELISA 测定上清液中的 IL-8 水平。最后,用递增剂量的地塞米松孵育 hNEC,并用台盼蓝和 Annexin-FITC/PI 染色以研究凋亡。

结果

从健康和 NP 患者的鼻甲和 NP 患者的息肉组织中分离的 hNEC 产生相似水平的 IL-8。IL-1β 在所有类型的 hNEC 中诱导更高水平的 IL-8 产生,且在对照和 NP 组织之间无差异。地塞米松诱导 hNEC 凋亡,同时阻断 hNEC 的 IL-8 产生。

结论

在基线和刺激条件下,NP 和健康组织中的人鼻腔上皮细胞产生的 IL-8 没有差异。地塞米松诱导 hNEC 凋亡并阻断 IL-8 产生。

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