Interleukin-17F induces pulmonary neutrophilia and amplifies antigen-induced allergic response
Interleukin-17F induces pulmonary neutrophilia and amplifies antigen-induced allergic response
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DOI：
10.1164/rccm.200406-778oc
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发表时间：
2005-01-01
影响因子：
24.7
通讯作者：
Huang, SK
中科院分区：
文献类型：
--
作者：
Oda, N;Canelos, PB;Huang, SK
白细胞介素(IL)-17F是最近描述的一种属于IL-17基因家族的人类细胞因子，但其体内功能仍有待确定。为此，首先鉴定了具有 483 bp 编码区序列的全长小鼠 IL-17F cDNA 序列。使用小鼠中 IL-17F 表达构建体 (pcDNAmIL-17F) 的肺部基因转移来研究其调节作用。结果首先表明，与模拟动物和磷酸盐缓冲盐水对照动物相比，IL-17F 转导小鼠的支气管肺泡灌洗液中中性粒细胞数量显着增加，同时编码 C-X-C 趋化因子和炎症细胞因子的基因表达增加。在抗原（Ag）攻击之前，卵清蛋白（OVA）致敏小鼠中IL-17F基因的粘膜转移增强了Ag诱导的肺中性粒细胞增多的水平，但不增强嗜酸性粒细胞增多、杯状细胞增生和粘蛋白基因表达。然而，Th2 细胞因子表达水平没有显着变化。在 IL-17F 转导的 Ag 致敏小鼠中还发现，吸入乙酰甲胆碱后通气时间显着增强，而在 IL-17F 转导的初始小鼠中发现了小但显着的增加。这些结果表明 IL-17F 在诱导肺部中性粒细胞增多和加剧 Ag 诱导的肺部炎症中发挥作用。
Interleukin (IL)-17F is a recently described human cytokine belonging to the IL-17 gene family, but its in vivo function remains to be determined. To this end, a full-length mouse IL-17F cDNA sequence with a 483-bp coding region sequence was first identified. Pulmonary gene transfer of an IL-17F expression construct (pcDNAmIL-17F) in mice was used to investigate its regulatory role. The results showed first that a significant increase in the number of neutrophils was seen in the bronchoalveolar lavage fluids of IL-17F-transduced mice, concomitant with increased expression of genes encoding C-X-C chemokines and inflammatory cytokines when compared with mock and phosphate-buffered saline control animals. Mucosal transfer of the IL-17F gene in ovalbumin (OVA)-sensitized mice before antigen (Ag) challenge enhanced the levels of Ag-induced pulmonary neutrophilia, but not eosinophilia, goblet cell hyperplasia, and mucin gene expression. However, no significant change in the levels of Th2 cytokine expression was noted. A significant enhancement of ventilatory timing in response to inhaled methacholine was also seen in IL-17F-transduced, Ag-sensitized mice, whereas a small but significant increase was found in IL-17F-transduced, naive mice. These results suggest a role for IL-17F in the induction of neutrophilia in the lungs and in the exacerbation of Ag-induced pulmonary inflammation.