Differential IL-6 and VEGF secretion in adult and neonatal mesenchymal stem cells: role of NFkB.
Stem cells have shown promise for the treatment of end organ ischemia. NFkB has been demonstrated to regulate growth factor secretion in human adult bone marrow stem cells (aBMSCs). We hypothesized that: (1) NFkB is an important mediator in aBMSC and neonatal BMSC (nBMSC) VEGF and IL-6 secretion; and (2) inhibition of NFkB will result in a decrease of VEGF and IL-6 in nBMSCs. BMSCs were plated and exposed to TNF (50 ng/ml) or LPS (100 ng/ml), with or without NFkB or IKK inhibition. VEGF and IL-6 were measured via ELISA in 24-h supernatants. Inhibition of NFkB and IKK both demonstrated a decrease in VEGF (p<0.05) in aBMSCs but not nBMSCs. The LPS-stimulated nBMSC with IKK inhibition group was the only exception which demonstrated a decrease in VEGF secretion. However, both NFkB inhibition caused both aBMSCs and nBMSCs to produced less IL-6 after LPS stimulation (p<0.05). Only aBMSCs' secretion of IL-6 decreased with NFkB and IKK inhibition when stimulated with TNF (p<0.05) differing only when TNF-stimulated nBMSCs were inhibited with IKK. VEGF and IL-6 secretion in aBMSCs is dependent on the classic NFkB pathway. However, neonatal BMSC VEGF and IL-6 secretion is stimulant-specific and utilization of the NFkB pathway is more complex.
Novotny
Nathan M
NM
Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Markel
Troy A
TA
Crisostomo
Paul R
PR
Meldrum
Daniel R
DR
D000375:Aging / Q000502:physiology*; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048069:Tumor Necrosis Factors / Q000494:pharmacology; D042442:Vascular Endothelial Growth Factors / Q000378:metabolism*
D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D048069:Tumor Necrosis Factors; D042442:Vascular Endothelial Growth Factors; D051550:I-kappa B Kinase