Activin A regulates activation of mouse neutrophils by Smad3 signalling

Open Biol. 2017 May;7(5):160342. doi: 10.1098/rsob.160342.

Abstract

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 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.

Keywords: Smad3; activin A; activin receptor; interleukin-6; neutrophils.

MeSH terms

  • Activin Receptors, Type II / genetics
  • Activin Receptors, Type II / metabolism
  • Activins / metabolism
  • Activins / pharmacology*
  • Animals
  • Cells, Cultured
  • Chemotaxis / genetics
  • Interleukin-6 / metabolism
  • Lipopolysaccharides / pharmacology
  • Male
  • Mice, Inbred C57BL
  • Neutrophils / cytology
  • Neutrophils / drug effects*
  • Neutrophils / metabolism
  • Phagocytosis / drug effects
  • Phosphorylation / drug effects
  • RNA Interference
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects*
  • Signal Transduction / genetics
  • Smad3 Protein / genetics
  • Smad3 Protein / metabolism*

Substances

  • Interleukin-6
  • Lipopolysaccharides
  • Reactive Oxygen Species
  • Smad3 Protein
  • Smad3 protein, mouse
  • activin A
  • Activins
  • Activin Receptors, Type II
  • activin receptor type II-A