Qi Yan, Ge Jingyan, Ma Chunhui, Wu Na, Cui Xueling, Liu Zhonghui
Department of Immunology, College of Basic Medical Sciences, Jilin University, Changchun 130021, People's Republic of China.
Key Laboratory of Neuroimmunology, College of Basic Medical Sciences, Jilin University, Changchun 130021, People's Republic of China.
Open Biol. 2017 May;7(5). doi: 10.1098/rsob.160342.
Activin A, a member of the transforming growth factor beta superfamily, acts as a pro-inflammatory factor in acute phase response, and influences the pathological progress of neutrophil-mediated disease. However, whether activin A can exert an effect on the activities of neutrophils remains unclear. In this study, we found that the release of activin A was enhanced from neutrophils of mouse when stimulated with lipopolysaccharide. Furthermore, neutrophils were not only the source of activin A but also the target cells in response to activin A, in which canonical activin signalling components existed, and levels of ACTRIIA, SMAD3 and p-SMAD3 proteins were elevated in activin A-treated neutrophils. Next, the role of activin A was determined in regulation of neutrophils activities. Our data revealed that activin A induced O release and reactive oxygen species production, promoted IL-6 release, and enhanced phagocytosis, but failed to attract neutrophils migrating across the trans-well membrane. Moreover, we found that effect of activin A on IL-6 release from the peritoneal neutrophils of mouse was significantly attenuated by knockdown. In summary, these data demonstrate that activin A can exert an effect on neutrophils activation in an autocrine/paracrine manner through Smad3 signalling, suggesting that activin A is an important regulator of neutrophils.
激活素A是转化生长因子β超家族的成员之一，在急性期反应中作为促炎因子发挥作用，并影响中性粒细胞介导疾病的病理进程。然而，激活素A是否能对中性粒细胞的活性产生影响仍不清楚。在本研究中，我们发现用脂多糖刺激时，小鼠中性粒细胞中激活素A的释放会增强。此外，中性粒细胞不仅是激活素A的来源，也是对激活素A产生反应的靶细胞，其中存在经典的激活素信号传导成分，在激活素A处理的中性粒细胞中，ACTRIIA、SMAD3和p-SMAD3蛋白的水平升高。接下来，我们确定了激活素A在调节中性粒细胞活性中的作用。我们的数据显示，激活素A诱导超氧阴离子释放和活性氧生成，促进白细胞介素-6释放，并增强吞噬作用，但未能吸引中性粒细胞穿过Transwell膜迁移。此外，我们发现通过基因敲低可显著减弱激活素A对小鼠腹腔中性粒细胞白细胞介素-6释放的影响。总之，这些数据表明激活素A可通过Smad3信号以自分泌/旁分泌方式对中性粒细胞激活产生影响，提示激活素A是中性粒细胞的重要调节因子。
