Abstract
The hMSCs have become a promising approach for inflammation treatment in acute phase. Our previous study has demonstrated that human umbilical cord-MSCs could alleviate the inflammatory reaction of severely burned wound. In this study, we further investigated the potential role and mechanism of the MSCs on severe burn-induced excessive inflammation. Wistar rats were randomly divided into following groups: Sham, Burn, Burn+MSCs, Burn+MAPKs inhibitors, and Burn, Burn+MSCs, Burn+Vehicle, Burn+siTSG-6, Burn+rhTSG-6 in the both experiments. It was found that MSCs could only down-regulate P38 and JNK signaling, but had no effect on ERK in peritoneal macrophages of severe burn rats. Furthermore, suppression of P38 and JNK activations significantly reduced the excessive inflammation induced by severe burn. TSG-6 was secreted by MSCs using different inflammatory mediators. TSG-6 from MSCs and recombinant human (rh)TSG-6 all significantly reduced activations of P38 and JNK signaling induced by severe burn and then attenuated excessive inflammations. On the contrary, knockdown TSG-6 in the cells significantly increased phosphorylation of P38 and JNK signaling and reduced therapeutic effect of the MSCs on excessive inflammation. Taken together, this study suggested TSG-6 from MSCs attenuated severe burn-induced excessive inflammation via inhibiting activation of P38 and JNK signaling.
Highlights
TSG-6 can suppress inflammatory reactions triggered by ischemia in the heart and thereby limit the destruction of cardiomyocytes by inhibiting neutrophils and monocytes/macrophages invading[18]
To investigate whether MSCs regulated the pro-inflammatory MAPKs signals or not, we examined the levels of phosphorylated P38, Jun N-terminus kinase (JNK), and extracellular signal regulated kinase (ERK) in the peritoneal macrophages at 24 h after burn by Western blotting
MSCs administration markedly down-regulated the phosphorylated levels of P38 and JNK but not phosphorylated ERK (p < 0.05)
Summary
TSG-6 can suppress inflammatory reactions triggered by ischemia in the heart and thereby limit the destruction of cardiomyocytes by inhibiting neutrophils and monocytes/macrophages invading[18]. MAPKs signaling play critical roles in regulation of inflammatory responses. The MAPKs including P38, c-Jun N-terminus kinase (JNK), and extracellular signal regulated kinase (ERK), were activated by cellular stress and proinflammatory cytokines[23]. Burned injury results in a cellular stress in the skin[24]. The P38 is activated in the skin wound after burned injury, whereas administration of P38 inhibitor in topical wound may reduce the adversely inflammatory responses[25]. Liu et al showed TSG-6 secreted by mesenchymal stem cells inhibited lipopolysaccharide-induced inflammatory responses of BV2 microglial cells through inhibiting the activation of nuclear factor (NF)-κB and MAPK pathways[26]. Based on the basis of our previous study, our present study was designed to further investigate the potential mechanism involving effects of human umbilical cord-MSCs on severe burn injury-induced excessive inflammation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
