Neutrophil recruitment by human IL-17 via C-X-C chemokine release in the airways.
Neutrophil recruitment by human IL-17 via C-X-C chemokine release in the airways.
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DOI：
10.4049/jimmunol.162.4.2347
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发表时间：
1999-02
影响因子：
4.4
通讯作者：
M. Laan;Zhan-Qun Cui;H. Hoshino;J. Lötvall;M. Sjöstrand;D. Gruenert;B. Skoogh;A. Lindén
中科院分区：
文献类型：
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作者：
M. Laan;Zhan-Qun Cui;H. Hoshino;J. Lötvall;M. Sjöstrand;D. Gruenert;B. Skoogh;A. Lindén
IL-17是新近发现的一种细胞因子，可从活化的人CD4+T淋巴细胞中释放出来。这项研究评估了人(H)IL-17在呼吸道中的促炎作用。在体外，hIL-17以时间和浓度依赖的方式增加人支气管上皮和静脉内皮细胞IL-8的释放。HIL-17的这种作用可被抗hIL-17抗体抑制，而被hTNF-α增强。此外，hIL-17还可增加支气管上皮细胞hIL-8mRNA的表达。经hIL-17处理的支气管上皮细胞条件培养液在体外促进人中性粒细胞迁移。这种作用可被抗hIL-8抗体阻断。在体内，气管内滴注hIL-17选择性地将中性粒细胞招募到大鼠呼吸道。中性粒细胞向呼吸道的这种募集被抗hIL-17抗体抑制，并伴随着BAL液中大鼠巨噬细胞炎性蛋白-2(rMIP-2)水平的增加。抗rMIP-2抗体也能阻断BAL的中性粒细胞。糖皮质激素在体外和体内均能抑制hIL-17对hIL-8和rMIP-2的释放。这些数据表明，hIL-17可以通过从支气管上皮细胞释放C-X-C趋化因子，特异性和选择性地将中性粒细胞招募到呼吸道，并提出了一种新的机制，将T淋巴细胞的激活与中性粒细胞向呼吸道的招募联系起来。
IL-17 is a recently discovered cytokine that can be released from activated human CD4+ T lymphocytes. This study assessed the proinflammatory effects of human (h) IL-17 in the airways. In vitro, hIL-17 increased the release of IL-8 in human bronchial epithelial and venous endothelial cells, in a time- and concentration-dependent fashion. This effect of hIL-17 was inhibited by cotreatment with an anti-hIL-17 Ab and was potentiated by hTNF-alpha. In addition, hIL-17 increased the expression of hIL-8 mRNA in bronchial epithelial cells. Conditioned medium from hIL-17-treated bronchial epithelial cells increased human neutrophil migration in vitro. This effect was blocked by an anti-hIL-8 Ab. In vivo, intratracheal instillation of hIL-17 selectively recruited neutrophils into rat airways. This recruitment of neutrophils into the airways was inhibited by an anti-hIL-17 Ab and accompanied by increased levels of rat macrophage inflammatory protein-2 (rMIP-2) in bronchoalveolar lavage (BAL) fluid. The BAL neutrophilia was also blocked by an anti-rMIP-2 Ab. The effect of hIL-17 on the release of hIL-8 and rMIP-2 was also inhibited by glucocorticoids, in vitro and in vivo, respectively. These data demonstrate that hIL-17 can specifically and selectively recruit neutrophils into the airways via the release of C-X-C chemokines from bronchial epithelial cells and suggest a novel mechanism linking the activation of T-lymphocytes to recruitment of neutrophils into the airways.