LPS- and LTA-induced expression of IL-6 and TNF-α in neonatal and adult blood: role of MAPKs and NF-κB

As nuclear factor kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) seem to be critical mediators in the inflammatory response, we studied the effects of lipopolysaccharide (LPS) and lipoteichoic acid (LTA) on (a) the activation of NF-κB and MAPKs and (b) the expression of tumor necrosis...

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Hauptverfasser: Koch, Lutz (VerfasserIn) , Frommhold, David (VerfasserIn) , Buschmann-Prayon, Kirsten (VerfasserIn) , Kuß, Navina (VerfasserIn) , Pöschl, Johannes (VerfasserIn) , Ruef, Peter (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 30 October 2014
In: Mediators of inflammation

ISSN:1466-1861
DOI:10.1155/2014/283126
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1155/2014/283126
Verlag, lizenzpflichtig, Volltext: https://www.hindawi.com/journals/mi/2014/283126/
Volltext
Verfasserangaben:Lutz Koch, David Frommhold, Kirsten Buschmann, Navina Kuss, Johannes Poeschl, and Peter Ruef

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520 |a As nuclear factor kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) seem to be critical mediators in the inflammatory response, we studied the effects of lipopolysaccharide (LPS) and lipoteichoic acid (LTA) on (a) the activation of NF-κB and MAPKs and (b) the expression of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) with or without the specific inhibitors of these intracellular signal transduction pathways in neonatal cord and adult blood. TNF-α and IL-6 concentrations showed a sharp increase in the supernatants of cord and adult whole blood after stimulation. TNF-α concentrations were significantly higher, whereas IL-6 concentrations were tendentially lower in adult blood after stimulation. Stimulation with LPS or LTA resulted in a significantly decreased activation of p38 MAPK in neonatal compared with adult blood. Although LTA failed to induce additional ERK1/2 phosphorylation, LPS stimulation mediated the moderately increased levels of activated ERK1/2 in neonatal monocytes. The addition of the p38 MAPK inhibitor SB202190 significantly decreased IL-6 and TNF-α production upon LPS or LTA stimulation. Furthermore, the inhibition of ERK1/2 was able to reduce LPS-stimulated TNF-α production in neonatal blood. We conclude that p38 MAPK as well as ERK1/2 phosphorylation is crucially involved in LPS activation and could explain the differences in early cytokine response between neonatal and adult blood. 
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