Differentiated transplant derived airway epithelial cell cytokine secretion is not regulated by cyclosporine.
Differentiated transplant derived airway epithelial cell cytokine secretion is not regulated by cyclosporine.
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DOI：
10.1186/1465-9921-12-44
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发表时间：
2011-04-10
影响因子：
5.8
通讯作者：
White SR
中科院分区：
文献类型：
--
作者：
Floreth T;Stern E;Tu Y;Stern R;Garrity ER Jr;Bhorade SM;White SR
尽管肺移植越来越多地用于晚期肺部疾病的治疗，但以闭塞性细支气管炎综合征（BOS）形式出现的慢性排斥反应仍会导致同种异体移植物功能障碍和患者死亡。尽管临床事件与BOS的最终发展存在相关性，但其致病病理生理机制尚不清楚。与BOS相关的炎症和纤维化区域内的气道上皮细胞可能具有参与作用。用IL-1β和/或环孢素处理经气液界面培养分化的移植源气道上皮细胞，分析细胞因子和生长因子的分泌以及上皮向间质转化标志物的基因表达。IL-1β刺激可增加IL-6、IL-8和TNF-α的分泌，但TGF-β1不增加。与之前使用上皮细胞浸泡培养的研究相比，在ALI培养中使用环孢素处理分化细胞不会引起细胞因子或生长因子的分泌，也不会改变IL-1β处理后IL-6、IL-8或TNF-α的产生。IL-1β和环孢素均未引起上皮向间质转化标志物e -钙粘蛋白、edn -纤维连接蛋白和α-平滑肌肌动蛋白的表达。体外环孢素不调节移植源分化气道上皮细胞IL-6、IL-8和TNF-α的分泌；因此，这些细胞可能在免疫抑制的情况下参与局部炎症反应。此外，用IL-1β治疗并没有引起上皮细胞向间充质细胞转化标记物的基因表达。这些数据提供了一个分化的气道上皮细胞模型，可能有助于理解上皮细胞参与气道炎症和肺移植中的同种异体移植排斥反应。
While lung transplantation is an increasingly utilized therapy for advanced lung diseases, chronic rejection in the form of Bronchiolitis Obliterans Syndrome (BOS) continues to result in significant allograft dysfunction and patient mortality. Despite correlation of clinical events with eventual development of BOS, the causative pathophysiology remains unknown. Airway epithelial cells within the region of inflammation and fibrosis associated with BOS may have a participatory role. Transplant derived airway epithelial cells differentiated in air liquid interface culture were treated with IL-1β and/or cyclosporine, after which secretion of cytokines and growth factor and gene expression for markers of epithelial to mesenchymal transition were analyzed. Secretion of IL-6, IL-8, and TNF-α, but not TGF-β1, was increased by IL-1β stimulation. In contrast to previous studies using epithelial cells grown in submersion culture, treatment of differentiated cells in ALI culture with cyclosporine did not elicit cytokine or growth factor secretion, and did not alter IL-6, IL-8, or TNF-α production in response to IL-1β treatment. Neither IL-1β nor cyclosporine elicited expression of markers of the epithelial to mesenchymal transition E-cadherin, EDN-fibronectin, and α-smooth muscle actin. Transplant derived differentiated airway epithelial cell IL-6, IL-8, and TNF-α secretion is not regulated by cyclosporine in vitro; these cells thus may participate in local inflammatory responses in the setting of immunosuppression. Further, treatment with IL-1β did not elicit gene expression of markers of epithelial to mesenchymal transition. These data present a model of differentiated airway epithelial cells that may be useful in understanding epithelial participation in airway inflammation and allograft rejection in lung transplantation.
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影响因子：
8.8
作者：
Neuringer, IP;Sloan, J;Randell, SH
通讯作者：
Randell, SH
影响因子：
6.4
作者：
Shen, L;Smith, JM;Fanger, MW
通讯作者：
Fanger, MW
影响因子：
5
作者：
Hetzel, M;Bachem, M;Faehling, M
通讯作者：
Faehling, M
DOI：
10.1513/pats.200801-010aw
发表时间：
2008-08-15
期刊：
Proceedings of the American Thoracic Society
影响因子：
--
作者：
Coraux, Christelle;Roux, Jacqueline;Birembaut, Philippe
通讯作者：
Birembaut, Philippe
影响因子：
24.3
作者：
Forrest, IA;Murphy, DM;Corris, PA
通讯作者：
Corris, PA