Cytokine interactions in mesenchymal stem cells from cord blood.
We used cytokine protein array to analyze the expression of cytokines from human cord blood-derived mesenchymal stem cells (CB-MSCs). Several cytokines, interleukins (IL), and growth factors, including ENA-78, GM-CSF, GRO, IL-1beta, IL-6, IL-8, MCP-1, OSM, VEGF, FGF-4, FGF-7, FGF-9, GCP-2, IGFBP-1, IGFBP-2, IGFBP-3, IGFBP-4, IP-10, LIF, MIF, MIP-3alpha, osteoprotegerin, PARC, PIGF, TGF-beta2, TGF-beta3, TIMP-1, as well as TIMP-2, were secreted by CB-MSCs, while IL-4, IL-5, IL-7, IL-13, TGF-beta1, TNF-alpha, and TNF-beta were not expressed under normal growth conditions. IL-6, IL-8, TIMP-1, and TIMP-2 were the most abundant interleukins expressed by CB-MSCs. A set of growth factors were selected to evaluate their stimulatory effects on the IL6 secretion for CB-MSCs. IL-1beta was the most important factor inducing CB-MSC to secret IL-6. The mechanism by which IL-1beta promoted IL-6 expression in CB-MSCs was studied. By using various inhibitors of signal transduction, we found that activation of p38 mitogen-activated protein kinases (MAPK) and MAPK kinase (MEK) is essential in the IL-1beta stimulated signaling cascade which leads to the increase in IL-6 synthesis. Additionally, continuous supplement of IL-1beta in the CB-MSCs culture will facilitate adipogenic maturation of CB-MSCs as evidenced by the presence of oil drops in the CB-MSCs and secretion of leptin, a molecule marker of adipocytes. These results strongly suggest that cytokine induction and signal transduction are important for the differentiation of CB-MSCs.
Liu
Chi-Hsien
CH
Graduate Institute of Biochemical and Biomedical Engineering, Chang Gung University, Taoyuan, Taiwan. chl@mail.cgu.edu.tw
Hwang
Shiaw-Min
SM
D043925:Angiogenesis Inducing Agents / Q000032:analysis; D000954:Antigens, Surface / Q000032:analysis; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D018925:Chemokines / Q000032:analysis; D017077:Culture Media, Conditioned / Q000737:chemistry; D016207:Cytokines / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005312:Fetal Blood / Q000166:cytology*; D005419:Flavonoids / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D006133:Growth Substances / Q000032:analysis / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007375:Interleukin-1 / Q000032:analysis / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism; D020738:Leptin / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D047495:PPAR gamma / Q000235:genetics; D011480:Protease Inhibitors / Q000032:analysis; D040081:Protein Array Analysis; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D017978:Receptors, Growth Factor / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D043925:Angiogenesis Inducing Agents; D000954:Antigens, Surface; D022782:CCAAT-Enhancer-Binding Protein-beta; D018925:Chemokines; D017077:Culture Media, Conditioned; D016207:Cytokines; D005419:Flavonoids; D006133:Growth Substances; D007093:Imidazoles; D007375:Interleukin-1; D015850:Interleukin-6; D020738:Leptin; D047495:PPAR gamma; D011480:Protease Inhibitors; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D017978:Receptors, Growth Factor; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one