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.
Highlights
Activins are members of the transforming growth factor beta (TGF-b) superfamily, and have pleiotropic roles in physiological and pathological processes including regulation of embryogenesis, induction of mesoderm, protection of neurons, tumorigenesis and control of immune response [1,2,3,4,5,6,7]
Neutrophils were stimulated with LPS as agonist, and tumour necrosis factor-a (TNF-a) and actvin A production were measured by enzyme-linked immunosorbent assay (ELISA)
The results revealed that ACTRIIA, SMAD3 and phosphorylated SMAD3 (p-SMAD3) levels increased obviously in nertrophils stimulated by activin A, suggesting that activin A may act as a regulator of neutrophils via ACTRIIA-SMAD3 signalling
Summary
Activins are members of the transforming growth factor beta (TGF-b) superfamily, and have pleiotropic roles in physiological and pathological processes including regulation of embryogenesis, induction of mesoderm, protection of neurons, tumorigenesis and control of immune response [1,2,3,4,5,6,7]. Like most other TGF-b family members, activins share homology and canonical Smad-mediated signalling pathway with TGF-b. They conduce signalling by binding to type II activin receptor (ACTRII), forming a ligand/ACTRII complex, the complex recruits type I activin receptor (ACTRI) to phosphorylates the recruited receptor-SMADs (SMAD2 and SMAD3) [11,12]. SMAD2/3 dissociate from the receptor, bind to SMAD4, the complex transmits the signal into the nucleus and promotes gene transcription [13,14,15]
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