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 activinA can exert an effect on the activities of neutrophils remains unclear. In this study,we found that the release of activinAwas enhanced from neutrophils of mouse when stimulated with lipopolysaccharide. Furthermore, neutrophils were not only the source of activinAbut 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 activinAwas determined in regulation of neutrophils activities. Our data revealed that activin A induced O2- 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 in vivo Smad3 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.
Qi, Y., Ge, J., Ma, C., Wu, N., Cui, X., & Liu, Z. (2017). Activin A regulates activation of mouse neutrophils by Smad3 signalling. Open Biology, 7(5). https://doi.org/10.1098/rsob.160342