TY - JOUR
T1 - Reactive bone marrow stromal cells attenuate systemic inflammation via sTNFR1
AU - Yagi, Hiroshi
AU - Soto-Gutierrez, Alejandro
AU - Navarro-Alvarez, Nalu
AU - Nahmias, Yaakov
AU - Goldwasser, Yoni
AU - Kitagawa, Yuko
AU - Tilles, Arno W.
AU - Tompkins, Ronald G.
AU - Parekkadan, Biju
AU - Yarmush, Martin L.
PY - 2010/10
Y1 - 2010/10
N2 - Excessive systemic inflammation following trauma, sepsis, or burn could lead to distant organ damage. The transplantation of bone marrow stromal cells or mesenchymal stem cells (MSCs) has been reported to be an effective treatment for several immune disorders by modulating the inflammatory response to injury. We hypothesized that MSCs can dynamically secrete systemic factors that can neutralize the activity of inflammatory cytokines. In this study, we showed that cocultured MSCs are able to decrease nuclear factor -B (NFB) activation in target epithelial cells incubated in inflammatory serum conditions. Proteomic screening revealed a responsive secretion of soluble tumor necrosis factor (TNF) receptor 1 (sTNFR1) when MSCs were exposed to lipopolysaccharide (LPS)-stimulated rat serum. The responsive effect was eliminated when NFB activation was blocked in MSCs. Intramuscular transplantation of MSCs in LPS-endotoxic rats decreased a panel of inflammatory cytokines and inflammatory infiltration of macrophages and neutrophils in lung, kidney, and liver when compared to controls. These results suggest that improvements of inflammatory responses in animal models after local transplantation of MSCs are at least, in part, explained by the NFB-dependent secretion of sTNFR1 by MSCs.
AB - Excessive systemic inflammation following trauma, sepsis, or burn could lead to distant organ damage. The transplantation of bone marrow stromal cells or mesenchymal stem cells (MSCs) has been reported to be an effective treatment for several immune disorders by modulating the inflammatory response to injury. We hypothesized that MSCs can dynamically secrete systemic factors that can neutralize the activity of inflammatory cytokines. In this study, we showed that cocultured MSCs are able to decrease nuclear factor -B (NFB) activation in target epithelial cells incubated in inflammatory serum conditions. Proteomic screening revealed a responsive secretion of soluble tumor necrosis factor (TNF) receptor 1 (sTNFR1) when MSCs were exposed to lipopolysaccharide (LPS)-stimulated rat serum. The responsive effect was eliminated when NFB activation was blocked in MSCs. Intramuscular transplantation of MSCs in LPS-endotoxic rats decreased a panel of inflammatory cytokines and inflammatory infiltration of macrophages and neutrophils in lung, kidney, and liver when compared to controls. These results suggest that improvements of inflammatory responses in animal models after local transplantation of MSCs are at least, in part, explained by the NFB-dependent secretion of sTNFR1 by MSCs.
UR - https://www.scopus.com/pages/publications/77957580211
U2 - 10.1038/mt.2010.155
DO - 10.1038/mt.2010.155
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AN - SCOPUS:77957580211
SN - 1525-0016
VL - 18
SP - 1857
EP - 1864
JO - Molecular Therapy
JF - Molecular Therapy
IS - 10
ER -
