Toll-like receptor triggering in cord blood mesenchymal stem cells.
Recently, the antagonizing effect on the differentiation of mesenchymal stem cells (MSCs) by toll-like receptor (TLR) ligands, was described. Our study shows that on more primitive cord blood derived MSCs, the expression of TLRs and ligand-induced triggering differs from that of bone marrow derived MSCs. At the RNA level, cord blood MSCs (unrestricted somatic stem cells; USSCs) express low levels of TLR1,3,5,9 and high levels of TLR4 and TLR6. At the protein level expression of TLR5 and very low expression of TLR4 was observed. NF-kappaB translocation studies revealed that both TLR4 and TLR5 are functional, although signalling kinetics induced by the individual ligands differed. Stimulation of USSCs with either lipopolysaccharide (LPS) or flagellin resulted in a marked increase of interleukin (IL)-6 and/or IL-8 production although levels differed significantly between both stimuli. Interestingly, tumour necrosis factor (TNF)-alpha was undetectable after TLR stimulation, which appeared to be due to an inactivated TNF-alpha promoter in USSCs. Moreover, osteoblastic differentiation was enhanced after triggering USSCs with LPS and flagellin. In summary, TLR4 and 5 signalling in USSCs is slow and results in the up-regulation of a restricted number of pro-inflammatory cytokines and enhanced osteoblastic differentiation. Apparently, the outcome of TLR signalling depends on the cell type that expresses them.
van den Berk
Lieke C J
LC
Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Geert Grooteplein, Nijmegen, The Netherlands.
Jansen
Bastiaan J H
BJ
Siebers-Vermeulen
Kim G C
KG
Netea
Mihai G
MG
Latuhihin
Talia
T
Bergevoet
Saskia
S
Raymakers
Reinier A
RA
Kögler
Gesine
G
Figdor
Carl C
CC
Adema
Gosse J
GJ
Torensma
Ruurd
R
D000818:Animals; D002454:Cell Differentiation; D005312:Fetal Blood / Q000166:cytology*; D005408:Flagellin / Q000378:metabolism; D007113:Immunity, Innate; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007700:Kinetics; D008070:Lipopolysaccharides / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D010006:Osteoblasts / Q000166:cytology; D011401:Promoter Regions, Genetic; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D051198:Toll-Like Receptor 5 / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015850:Interleukin-6; D016209:Interleukin-8; D008070:Lipopolysaccharides; C495345:TLR4 protein, human; C495346:TLR5 protein, human; D051197:Toll-Like Receptor 4; D051198:Toll-Like Receptor 5; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D005408:Flagellin