Up-regulation of production of TGF-β and IL-4 and down-regulation of IL-6 by apoptotic human bronchial epithelial cells
Up-regulation of production of TGF-β and IL-4 and down-regulation of IL-6 by apoptotic human bronchial epithelial cells
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DOI：
10.1046/j.1440-1711.2002.01120.x
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发表时间：
2002-12-01
影响因子：
4
通讯作者：
Holmes, M
中科院分区：
文献类型：
--
作者：
Hodge, S;Hodge, G;Holmes, M
人支气管上皮细胞分泌细胞因子，在肺免疫应答中发挥作用。然而，这些细胞因子在调节急性肺损伤后上皮修复中的作用在很大程度上是未知的。对损伤的反应包括上皮细胞增生和鳞状化生。消退期以增生停止为特征。细胞凋亡被认为是清除不需要细胞而不引起炎症的最有效的机制。tgf - β 1的存在增加了气道上皮细胞的凋亡，诱导了鳞状化生，抑制了气道上皮细胞的增殖。白细胞介素-4增加巨噬细胞吞噬上皮细胞和产生炎性细胞因子的能力。本研究的目的是探讨急性肺损伤后肺上皮细胞凋亡产生细胞因子的假说，细胞因子可以自分泌控制肺增生，诱导肺鳞状分化。以支气管上皮细胞系（16hbe）为体外模型，研究肺上皮细胞凋亡过程中tgf - β、IL-4和IL-6的产生。采用fitc偶联膜联蛋白V进行亮染色和阴性染色，分别对凋亡细胞和活细胞进行分类。流式细胞术检测细胞内IL-6、tgf - β和IL-4。电镜、免疫组化、酶联免疫吸附试验为支持技术。凋亡细胞比活细胞产生更多的tgf - β和IL-4（但较少的IL-6）。在急性肺损伤中，凋亡上皮细胞增加tgf - β和IL-4的产生可能有助于抑制增殖、鳞状化生和减轻炎症反应。
Human bronchial epithelial cells secrete cytokines that play a role in immune responses in the lung. However, the roles of these cytokines in regulating epithelial repair following acute lung injury are largely unknown. Responses to injury include hyperplasia of epithelial cells and squamous metaplasia. The resolution stage is characterized by discontinuation of hyperplasia. Apoptosis is considered to be the most efficient mechanism of removal of unwanted cells without causing inflammation. The presence of TGF-beta1 increases apoptosis, induces squamous metaplasia and inhibits proliferation of airway epithelial cells. Interleukin-4 increases the ability of macrophages to phagocytose epithelial cells and produce inflammatory cytokines. The purpose of this study was to investigate the hypothesis that apoptotic lung epithelial cells produce cytokines, which could act in an autocrine manner to control hyperplasia and induce squamous differentiation following acute lung injury. A bronchial epithelial cell line (16 HBE) was used as an in vitro model, to study the production of TGF-beta, IL-4 and IL-6 by lung epithelial cells undergoing apoptosis. Apoptotic and live cells were sorted on the basis of bright and negative staining with FITC-conjugated Annexin V, respectively. Intracellular IL-6, TGF-beta and IL-4 was measured using flow cytometric techniques. Electron microscopy, immunohistochemistry and ELISA were used as supportive techniques. Apoptotic cells produced significantly more TGF-beta and IL-4 (but less IL-6) than viable cells. Increased production of TGF-beta and IL-4 by epithelial cells undergoing apoptosis may contribute to the inhibition of proliferation, squamous metaplasia, and reduction of the inflammatory response in acute lung injury.