Central Nervous System inflammation is primarily driven by microglial cells which secrete proinflammatory cytokines and undergo proliferation upon activation, as it occurs in neurodegenerative diseases. Uncontrolled or prolonged CNS inflammation is potentially harmful and can result in cellular damage. Recently, many studies have focused on human adipose tissue as an attractive source of cytokines with immunosuppressive properties that potentially modulate inflammation. Our study aimed to evaluate if different methods of human tissue collection could affect adipose mesenchymal stem cells (ADSC)-derived cytokine secretion, to investigate the effects of ADSC secretome in modulating microglia activation, and the possible implication of sphingosine-1-phosphate (S1P) in these effects. Our results demonstrate that the conditioned medium of ADSCs isolated by two different processing methods (lipoaspirate and Lipogems) significantly inhibited the LPS-induced effects on microglia activation, including microglial expression of CD68, cytokine secretion, proliferation, and migration. Pulse studies with radiolabeled sphingosine demonstrated that LPS treatment of resting microglia induced a significant increase of both cellular, and extracellular S1P. Moreover, and of relevance, FTY720, a functional antagonist of S1P receptor, inhibited the multiple LPS-induced pro-inflammatory effects on microglia, and S1P suppressed the anti-inflammatory effect of ADSC-CM. This suggests that LPS-mediated microglial activation is countered by ADSC-CM via the modulation of sphingosine kinase/S1P signalling.
The adipose mesenchymal stem cell secretome inhibits inflammatory responses of microglia: evidence for an involvement of sphingosine-1-phosphate signalling
Fassina L;
2016-01-01
Abstract
Central Nervous System inflammation is primarily driven by microglial cells which secrete proinflammatory cytokines and undergo proliferation upon activation, as it occurs in neurodegenerative diseases. Uncontrolled or prolonged CNS inflammation is potentially harmful and can result in cellular damage. Recently, many studies have focused on human adipose tissue as an attractive source of cytokines with immunosuppressive properties that potentially modulate inflammation. Our study aimed to evaluate if different methods of human tissue collection could affect adipose mesenchymal stem cells (ADSC)-derived cytokine secretion, to investigate the effects of ADSC secretome in modulating microglia activation, and the possible implication of sphingosine-1-phosphate (S1P) in these effects. Our results demonstrate that the conditioned medium of ADSCs isolated by two different processing methods (lipoaspirate and Lipogems) significantly inhibited the LPS-induced effects on microglia activation, including microglial expression of CD68, cytokine secretion, proliferation, and migration. Pulse studies with radiolabeled sphingosine demonstrated that LPS treatment of resting microglia induced a significant increase of both cellular, and extracellular S1P. Moreover, and of relevance, FTY720, a functional antagonist of S1P receptor, inhibited the multiple LPS-induced pro-inflammatory effects on microglia, and S1P suppressed the anti-inflammatory effect of ADSC-CM. This suggests that LPS-mediated microglial activation is countered by ADSC-CM via the modulation of sphingosine kinase/S1P signalling.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
