Interleukin-1 Family Member 9 Stimulates Chemokine Production and Neutrophil Influx in Mouse Lungs
Interleukin-1 Family Member 9 Stimulates Chemokine Production and Neutrophil Influx in Mouse Lungs
复制标题
DOI：
10.1165/rcmb.2009-0315oc
复制
发表时间：
2011-02-01
影响因子：
6.4
通讯作者：
LeVine, Ann Marie
中科院分区：
文献类型：
--
作者：
Ramadas, Ravisankar A.;Ewart, Susan L.;LeVine, Ann Marie
白细胞介素-1 （IL-1）是一种促炎细胞因子，通过I型IL-1受体（IL-1RI）发出信号。最近发现了新的il -1样细胞因子。它们在肺部疾病中的功能尚不清楚。白细胞介素-1家族成员-9 （IL-1F9）是一种类似il -1的细胞因子，在人类和小鼠的肺中表达。IL-1F9通过IL-1受体相关蛋白2 （IL-1Rrp2/IL-1RL2）发出信号，与IL-1RI不同。我们试图确定IL-1F9是否在肺部疾病中作为促炎细胞因子。与对照组相比，屋尘螨攻毒A/J小鼠肺匀浆中IL-1F9蛋白表达增加，并在气道上皮细胞中表达。气管内给药重组小鼠IL-1F9增加气道高反应性，诱导中性粒细胞内流和粘液产生，但不增加小鼠肺部嗜酸性粒细胞浸润。此外，气管内注入IL-1F9后，支气管肺泡灌洗液中IL-1 α蛋白水平、肺内趋化因子及趋化因子受体mRNA表达均升高。与这些变化一致的是，在IL-1F9刺激小鼠的肺部和IL-1F9处理的巨噬细胞系中，nf - κ B转录因子活性增加。这些数据表明，IL-1F9在炎症期间上调，并在肺中充当促炎细胞因子。
Interleukin-1 (IL-1) is a proinflammatory cytokine that signals through the Type I IL-1 receptor (IL-1RI). Novel IL-1-like cytokines were recently identified. Their functions in lung disease remain unclear. Interleukin-1 family member-9 (IL-1F9) is one such IL-1-like cytokine, expressed in the lungs of humans and mice. IL-1F9 signals through IL-1 receptor-related protein 2 (IL-1Rrp2/IL-1RL2), which is distinct from IL-1RI. We sought to determine if IL-1F9 acts as a proinflammatory cytokine in lung disease. IL-1F9 protein was increased in lung homogenates of house dust mite-challenged A/J mice compared with controls, and expression was seen in airway epithelial cells. The intratracheal administration of recombinant mouse IL-1F9 increased airway hyperresponsiveness and induced neutrophil influx and mucus production, but not eosinophilic infiltration in the lungs of mice. In addition, IL-1 alpha protein levels in bronchoalveolar lavage fluid, chemokines, and chemokine-receptor mRNA expression in the lungs were increased after the instillation of intratracheal IL-1F9. Consistent with these changes, NF-kappa B transcription factor activity was increased in the lungs of mice challenged with IL-1F9 and in a macrophage cell line treated with IL-1F9. These data suggest that IL-1F9 is upregulated during inflammation, and acts as a proinflammatory cytokine in the lungs.