title: TSG-6 secreted by human umbilical cord-MSCs attenuates severe burn-induced excessive inflammation via inhibiting activations of P38 and JNK signaling.
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.
authors.affiliation: Department of Burn &Plastic Surgery, the First Affiliated Hospital to PLA General Hospital.
authors.forename: Lingying
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Burn &Plastic Surgery, the First Affiliated Hospital to PLA General Hospital.
authors.forename: Huifeng
authors.initials: H
authors.lastname: Song
authors.affiliation: Department of Burn &Plastic Surgery, the First Affiliated Hospital to PLA General Hospital.
authors.forename: Hongjie
authors.initials: H
authors.lastname: Duan
authors.affiliation: Department of Burn &Plastic Surgery, the First Affiliated Hospital to PLA General Hospital.
authors.forename: Jiake
authors.initials: J
authors.lastname: Chai
authors.affiliation: Department of Burn &Plastic Surgery, the First Affiliated Hospital to PLA General Hospital.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Burn &Plastic Surgery, the First Affiliated Hospital to PLA General Hospital.
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Burn &Plastic Surgery, the First Affiliated Hospital to PLA General Hospital.
authors.forename: Yonghui
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Burn &Plastic Surgery, the First Affiliated Hospital to PLA General Hospital.
authors.forename: Xulong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Burn &Plastic Surgery, the First Affiliated Hospital to PLA General Hospital.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Burn &Plastic Surgery, the First Affiliated Hospital to PLA General Hospital.
authors.forename: Mengjing
authors.initials: M
authors.lastname: Xiao
authors.affiliation: Department of Burn &Plastic Surgery, the First Affiliated Hospital to PLA General Hospital.
authors.forename: Rui
authors.initials: R
authors.lastname: Feng
authors.affiliation: Department of Burn &Plastic Surgery, the First Affiliated Hospital to PLA General Hospital.
authors.forename: Huinan
authors.initials: H
authors.lastname: Yin
authors.affiliation: Department of Burn &Plastic Surgery, the First Affiliated Hospital to PLA General Hospital.
authors.forename: Quan
authors.initials: Q
authors.lastname: Hu
authors.affiliation: Department of Burn &Plastic Surgery, the First Affiliated Hospital to PLA General Hospital.
authors.forename: Longlong
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Burn &Plastic Surgery, the First Affiliated Hospital to PLA General Hospital.
authors.forename: Jundong
authors.initials: J
authors.lastname: Du
authors.affiliation: Department of Burn &Plastic Surgery, the First Affiliated Hospital to PLA General Hospital.
authors.forename: Tianran
authors.initials: T
authors.lastname: Li
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002056:Burns / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002478:Cells, Cultured; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014470:Umbilical Cord / Q000187:drug effects / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D015815:Cell Adhesion Molecules; D047428:Protein Kinase Inhibitors; C072273:TNFAIP6 protein, human; D048051:p38 Mitogen-Activated Protein Kinases