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Status: Bibliographieeintrag

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Verfasst von:Beuke, Katharina [VerfasserIn]   i
 Pinna, Federico [VerfasserIn]   i
 Liebe, Roman [VerfasserIn]   i
 Bissinger, Michaela [VerfasserIn]   i
 Schirmacher, Peter [VerfasserIn]   i
 Dooley, Steven [VerfasserIn]   i
 Kummer, Ursula [VerfasserIn]   i
 Breuhahn, Kai [VerfasserIn]   i
 Sahle, Sven [VerfasserIn]   i
Titel:Quantitative and integrative analysis of paracrine hepatocyte activation by nonparenchymal cells upon lipopolysaccharide induction
Verf.angabe:Katharina Beuke, Frank A. Schildberg, Federico Pinna, Ute Albrecht, Roman Liebe, Michaela Bissinger, Peter Schirmacher, Steven Dooley, Johannes G. Bode, Percy A. Knolle, Ursula Kummer, Kai Breuhahn and Sven Sahle
E-Jahr:2017
Jahr:21 January 2017
Umfang:18 S.
Fussnoten:Gesehen am 13.06.2018
Titel Quelle:Enthalten in: Vereinigung der Europäischen Biochemischen GesellschaftenThe FEBS journal
Ort Quelle:Oxford [u.a.] : Wiley-Blackwell, 2005
Jahr Quelle:2017
Band/Heft Quelle:284(2017), 5, Seite 796-813
ISSN Quelle:1742-4658
Abstract:Gut-derived bacterial lipopolysaccharides (LPS) stimulate the secretion of tumour necrosis factor (TNF) from liver macrophages (MCs), liver sinusoidal endothelial cells (LSECs) and hepatic stellate cells (HSCs), which control the acute phase response in hepatocytes through activation of the NF-κB pathway. The individual and cooperative impact of nonparenchymal cells on this clinically relevant response has not been analysed in detail due to technical limitations. To gain an integrative view on this complex inter- and intracellular communication, we combined a multiscale mathematical model with quantitative, time-resolved experimental data of different primary murine liver cell types. We established a computational model for TNF-induced NF-κB signalling in hepatocytes, accurately describing dose-responsiveness for physiologically relevant cytokine concentrations. TNF secretion profiles were quantitatively measured for all nonparenchymal cell types upon LPS stimulation. This novel approach allowed the analysis of individual and collective paracrine TNF-mediated NF-κB induction in hepatocytes, revealing strongest effects of MCs and LSECs on hepatocellular NF-κB signalling. Simulations suggest that both cell types act together to maximize the NF-κB pathway response induced by low LPS concentrations (0.1 and 1 ng/mL). Higher LPS concentrations (≥ 5 ng/mL) induced sufficient TNF levels from MCs or LSECs to induce a strong and nonadjustable pathway response. Importantly, these simulations also revealed that the initial cytokine secretion (1-2 h after stimulation) rather than final TNF level (10 h after stimulation) defines the hepatocellular NF-κB response. This raises the question whether the current experimental standard of single high-dose cytokine administration is suitable to mimic in vivo cytokine exposure. Database The computational models described in this manuscript are available in the JWS database via the following link: https://jjj.bio.vu.nl/database/beuke
DOI:doi:10.1111/febs.14022
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

kostenfrei: Volltext: http://dx.doi.org/10.1111/febs.14022
 kostenfrei: Volltext: https://febs.onlinelibrary.wiley.com/doi/abs/10.1111/febs.14022
 DOI: https://doi.org/10.1111/febs.14022
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:cytokine secretion
 hepatic stellate cells
 inflammation
 lipopolysaccharide
 liver
 liver sessile macrophages
 liver sinusoidal endothelial cells
 nuclear factor kappa B
 ODE model
 tumour necrosis factor
K10plus-PPN:1576304817
Verknüpfungen:→ Zeitschrift

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