IL-17, produced by lymphocytes and neutrophils, is necessary for lipopolysaccharide-induced airway neutrophilia: IL-15 as a possible trigger
IL-17, produced by lymphocytes and neutrophils, is necessary for lipopolysaccharide-induced airway neutrophilia: IL-15 as a possible trigger
复制标题
DOI：
10.4049/jimmunol.170.4.2106
复制
发表时间：
2003-02-15
影响因子：
4.4
通讯作者：
Trifilieff, A
中科院分区：
文献类型：
--
作者：
Ferretti, S;Bonneau, O;Trifilieff, A
IL-17是参与炎症调节的细胞因子。我们使用LPS诱导的小鼠肺部炎症模型研究了这种细胞因子在中性粒细胞募集中的作用。在支气管肺泡灌洗中，LPS诱导中性粒细胞第一波涌入，在第1天达到峰值，随后是第二波，在第2天达到峰值。IL-17水平在嗜中性粒细胞晚期（第2天）增加，这伴随着T细胞和巨噬细胞数量的增加，以及肺组织中KC和巨噬细胞炎性蛋白-2水平的增加。用中和鼠抗IL-17 Ab鼻内处理抑制晚期嗜中性粒细胞。在支气管肺泡灌洗液细胞中，IL-17 mRNA在激发后第1、2和3天检测到，在第2天强表达。这种表达与CD 4（+）和CD 8（+）细胞有关，但也与中性粒细胞有关。当用LPS攻击时，尽管缺乏T细胞，但SCID小鼠也产生与IL-17产生相关的嗜酸性应答。在BALB/c小鼠，IL-15 mRNA，主要与中性粒细胞，证明后1天LIPS的挑战。在体外，IL-15能够诱导纯化的脾CD 4（+）细胞释放IL-17，但不能诱导脾CD 8（+）或气道中性粒细胞释放IL-17。我们已经证明，IL-17主要由CD 4（+）细胞产生，但也由中性粒细胞产生，在细菌攻击后肺中性粒细胞的动员中起作用。此外，我们的研究结果表明，IL-15可能代表一种生理触发，导致细菌感染后IL-17的产生。
IL-17 is a cytokine implicated in the regulation of inflammation. We investigated the role of this cytokine in neutrophil recruitment using a model of LPS-induced lung inflammation in mice. In the bronchoalveolar lavage, LPS induced a first influx of neutrophils peaking at day 1, followed by a second wave, peaking at day 2. IL-17 levels were increased during the late phase neutrophilia (day 2), and this was concomitant with an increased number of T cells and macrophages, together with an increase of KC and macrophage-inflammatory protein-2 levels in the lung tissue. Intranasal treatment with a neutralizing murine anti-IL-17 Ab inhibited the late phase neutrophilia. In the bronchoalveolar lavage cells, IL-17 mRNA was detected at days 1, 2, and 3 post-challenge, with a strong expression at day 2. This expression was associated with CD4(+) and CD8(+) cells, but also with neutrophils. When challenged with LPS, despite the absence of T cells, SCID mice also developed a neutrophilic response associated with IL-17 production. In BALB/c mice, IL-15 mRNA, associated mainly with neutrophils, was evidenced 1 day after LIPS challenge. In vitro, IL-15 was able to induce IL-17 release from purified spleen CD4(+) cells, but not spleen CD8(+) or airway neutrophils. We have shown that IL-17, produced mainly by CD4(+) cells, but also by neutrophils, plays a role in the mobilization of lung neutrophils following bacterial challenge. In addition, our results suggest that IL-15 could represent a physiological trigger that leads to IL-17 production following bacterial infection.