TRAF1 regulates recruitment of lymphocytes and, to a lesser extent, neutrophils, myeloid dendritic cells and monocytes to the lung airways following lipopolysaccharide inhalation.
TRAF1 regulates recruitment of lymphocytes and, to a lesser extent, neutrophils, myeloid dendritic cells and monocytes to the lung airways following lipopolysaccharide inhalation.
复制标题
TRAF1 调节吸入脂多糖后淋巴细胞的募集，并在较小程度上调节中性粒细胞、骨髓树突细胞和单核细胞向肺气道的募集。
DOI：
10.1111/j.1365-2567.2006.02499.x
复制
发表时间：
2007
期刊：
影响因子：
6.4
通讯作者：
Tsitsikov,ErdyniN
中科院分区：
文献类型：
--
作者：
Oyoshi,MichikoK;Barthel,Robert;Tsitsikov,ErdyniN
吸入性脂多糖（LPS）诱导的炎症反应可能有助于哮喘和其他气道疾病的发病机制。在这里，我们使用LPS诱导的小鼠肺部炎症模型研究肿瘤坏死因子（TNF）受体相关因子1（TRAF 1）在白细胞募集中的作用。TRAF 1-/-小鼠在吸入LPS后完全缺乏淋巴细胞向下呼吸道的募集。尽管TRAF 1-/-小鼠在肺泡空气中显示出正常的中性粒细胞、树突状细胞和单核细胞的早期积累，但与野生型（WT）小鼠相比，在吸入LPS后24小时，这些细胞的募集显著减少。 尽管LPS处理后促炎细胞因子TNF、白细胞介素1（IL-1）和IL-6的表达正常，但与LPS处理的WT小鼠相比，TRAF 1-/-小鼠肺中细胞间粘附分子1、血管细胞粘附分子1、CCL 17和CCL 20的表达降低。这些结果表明TRAF 1通过增加趋化因子和粘附分子的表达促进LPS诱导的白细胞募集到肺气道中。缺乏TNF受体1（TNFR 1）但不缺乏TNFR 2的小鼠表现出与TRAF 1-/-小鼠相似的表型，表明TRAF 1可能在TNFR 1下游起作用。值得注意的是，我们使用骨髓嵌合体来证明TRAF 1由驻留在肺中的细胞表达，而不是由循环白细胞表达，对于LPS诱导的白细胞向肺气道的有效募集是必要的。
Inhaled lipopolysaccharide (LPS) induces an inflammatory response that may contribute to the pathogenesis of asthma and other airway diseases. Here we investigate the role of tumour necrosis factor (TNF) receptor‐associated factor 1 (TRAF1) in leucocyte recruitment using a model of LPS‐induced lung inflammation in mice. TRAF1–/–mice are completely deficient in the recruitment of lymphocytes to the lower respiratory tract after inhalation of LPS. Although TRAF1–/–mice display normal early accumulation of neutrophils, dendritic cells and monocytes in the alveolar airspace, they have a significantly reduced recruitment of these cells by 24 hr after inhalation of LPS when compared to wild‐type (WT) mice. Despite normal expression of the pro‐inflammatory cytokines TNF, interleukin‐1 (IL‐1) and IL‐6 after LPS treatment, TRAF1–/–mice displayed decreased expression of intercellular adhesion molecule 1, vascular cell adhesion molecule 1, CCL17 and CCL20 in the lungs, when compared to LPS‐treated WT mice. These results suggest that TRAF1 facilitates LPS‐induced leucocyte recruitment into the lung airways by augmenting the expression of chemokines and adhesion molecules. Mice lacking TNF receptor 1 (TNFR1) but not TNFR2 show a phenotype similar to the TRAF1–/–mice, suggesting that TRAF1 may act downstream of TNFR1. Significantly, we use bone marrow chimeras to demonstrate that expression of TRAF1 by cells resident in the lungs, but not by circulating leucocytes, is necessary for efficient LPS‐induced recruitment of leucocytes to the lung airways.