Laan M, Cui Z H, Hoshino H, Lötvall J, Sjöstrand M, Gruenert D C, Skoogh B E, Lindén A
Lung Pharmacology Group, Department of Respiratory Medicine and Allergology, Göteborg University, Sweden.
J Immunol. 1999 Feb 15;162(4):2347-52.
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.
白细胞介素-17是一种最近发现的细胞因子，可从活化的人CD4 + T淋巴细胞中释放出来。本研究评估了人（h）白细胞介素-17在气道中的促炎作用。在体外，hIL-17以时间和浓度依赖性方式增加人支气管上皮细胞和静脉内皮细胞中IL-8的释放。hIL-17的这种作用被抗hIL-17抗体共同处理所抑制，并被hTNF-α增强。此外，hIL-17增加了支气管上皮细胞中hIL-8 mRNA的表达。hIL-17处理的支气管上皮细胞的条件培养基在体外增加了人中性粒细胞的迁移。这种作用被抗hIL-8抗体阻断。在体内，气管内滴注hIL-17可选择性地将中性粒细胞募集到大鼠气道中。这种中性粒细胞向气道的募集被抗hIL-17抗体抑制，并伴有支气管肺泡灌洗（BAL）液中大鼠巨噬细胞炎性蛋白-2（rMIP-2）水平的升高。BAL中的中性粒细胞增多也被抗rMIP-2抗体阻断。hIL-17对hIL-8和rMIP-2释放的作用在体外和体内分别也被糖皮质激素抑制。这些数据表明，hIL-17可通过从支气管上皮细胞释放C-X-C趋化因子，特异性地和选择性地将中性粒细胞募集到气道中，并提示了一种将T淋巴细胞活化与中性粒细胞募集到气道中联系起来的新机制。
