Mesenchymal stem cells respond to TNF but do not produce TNF.
Previously, we demonstrated that several TLRs are expressed on cord blood-derived USSC. Stimulation of USSC with TLR agonists resulted in a marked increase of IL-6 and IL-8 production. Interestingly, TNF was undetectable after TLR stimulation, which appeared to be a result of an inactivated TNF promoter in USSC. Here, we elaborate this study by demonstrating that although USSC do not produce TNF, they are susceptible to TNF stimulation, resulting in NF-kappaB translocation and cytokine production. Additionally, we compared different stem cell sources for their ability to produce TNF. Interestingly, we found that the TNF promoter in BM-MSC is inactivated as well. Like USSC, they are able to respond to TNF stimulation, but they are not able to produce TNF, even not after LPS stimulation. This limited cytokine response in combination with the well-studied immunosuppressive properties of MSC makes these cells ideal for immune-suppressive treatment modalities such as graft-versus-host disease.
van den Berk
Lieke C J
LC
Department of Tumor Immunology, Radboud University Nijmegen Medical Centre, Geert Grooteplein 28, 6525 GA Nijmegen, the Netherlands.
Jansen
Bastiaan J H
BJ
Siebers-Vermeulen
Kim G C
KG
Roelofs
Helene
H
Figdor
Carl G
CG
Adema
Gosse J
GJ
Torensma
Ruurd
R
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D002460:Cell Line; D002467:Cell Nucleus / Q000276:immunology / Q000378:metabolism; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology*; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D016209:Interleukin-8 / Q000276:immunology / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology*
C508606:CXCL8 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha