prikaz prve stranice dokumenta LPS‐induced inflammation desensitizes hepatocytes to Fas‐induced apoptosis through Stat3 activation—The effect can be reversed by ruxolitinib
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Scientific paper - Original scientific paper
LPS‐induced inflammation desensitizes hepatocytes to Fas‐induced apoptosis through Stat3 activation—The effect can be reversed by ruxolitinib
Journal of Cellular and Molecular Medicine, 24 (2020), 5; 2981-2992. https://doi.org/10.1111/jcmm.14930
Markotić, Antonio; Flegar, Darja; Grčević, Danka; Šućur, Alan; Lalić, Hrvoje; Turčić, Petra; Kovačić, Nataša; Lukač, Nina; Pravdić, Danijel; Vukojević, Katarina; Čavar, Ivan; Kelava, Tomislav

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Markotić, A., Flegar, D., Grčević, D., Šućur, A., Lalić, H., Turčić, P. ... Kelava, T. (2020). LPS‐induced inflammation desensitizes hepatocytes to Fas‐induced apoptosis through Stat3 activation—The effect can be reversed by ruxolitinib. Journal of Cellular and Molecular Medicine, 24. (5), 2981-2992. doi: 10.1111/jcmm.14930

Markotić, Antonio, et al. "LPS‐induced inflammation desensitizes hepatocytes to Fas‐induced apoptosis through Stat3 activation—The effect can be reversed by ruxolitinib." Journal of Cellular and Molecular Medicine, vol. 24, no. 5, 2020, pp. 2981-2992. https://doi.org/10.1111/jcmm.14930

Markotić, Antonio, Darja Flegar, Danka Grčević, Alan Šućur, Hrvoje Lalić, Petra Turčić, Nataša Kovačić, et al. "LPS‐induced inflammation desensitizes hepatocytes to Fas‐induced apoptosis through Stat3 activation—The effect can be reversed by ruxolitinib." Journal of Cellular and Molecular Medicine 24, no. 5 (2020): 2981-2992. https://doi.org/10.1111/jcmm.14930

Markotić, A., et al. (2020) 'LPS‐induced inflammation desensitizes hepatocytes to Fas‐induced apoptosis through Stat3 activation—The effect can be reversed by ruxolitinib', Journal of Cellular and Molecular Medicine, 24(5), pp. 2981-2992. doi: 10.1111/jcmm.14930

Markotić A, Flegar D, Grčević D, Šućur A, Lalić H, Turčić P, and sur.. LPS‐induced inflammation desensitizes hepatocytes to Fas‐induced apoptosis through Stat3 activation—The effect can be reversed by ruxolitinib. Journal of Cellular and Molecular Medicine [Internet]. 2020 March [cited 2024 April 13];24(5):2981-2992. doi: 10.1111/jcmm.14930

A. Markotić, et al., "LPS‐induced inflammation desensitizes hepatocytes to Fas‐induced apoptosis through Stat3 activation—The effect can be reversed by ruxolitinib", Journal of Cellular and Molecular Medicine, vol. 24, no. 5, pp. 2981-2992, March 2020. [Online]. Available at: https://urn.nsk.hr/urn:nbn:hr:105:210422. [Accessed: 13 April 2024]

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Title (english)LPS‐induced inflammation desensitizes hepatocytes to Fas‐induced apoptosis through Stat3 activation—The effect can be reversed by ruxolitinib
AuthorAntonio Markotić
AuthorDarja Flegar
AuthorDanka Grčević
AuthorAlan Šućur
AuthorHrvoje Lalić
AuthorPetra Turčić
AuthorNataša Kovačić
AuthorNina Lukač
AuthorDanijel Pravdić
AuthorKatarina Vukojević
AuthorIvan Čavar
AuthorTomislav Kelava
Author's institutionUniversity of Zagreb
School of Medicine
Scientific / art field,
discipline and subdiscipline		BIOMEDICINE AND HEALTHCARE
Basic Medical Sciences
Anatomy
Scientific / art field,
discipline and subdiscipline		BIOMEDICINE AND HEALTHCARE
Basic Medical Sciences
Human Physiology
Abstract (croatian)
Recent studies have established a concept of tumour necrosis factor-α (TNF-α)/Fas signalling crosstalk, highlighting TNF-α as a critical cytokine in sensitizing hepatocytes to death induced by Fas activation. However, in the exact inflammatory response, besides TNF-α, many other mediators, that might modulate apoptotic response differentially, are released. To resolve the issue, we studied the effects of lipopolysaccharide (LPS), one of the crucial inductors of inflammation in the liver, on apoptotic outcome. We show that LPS-induced inflammation diminishes the sensitivity of hepatocytes to Fas stimulus in vivo at caspase-8 level. Analysis of molecular mechanisms revealed an increased expression of various pro-inflammatory cytokines in non-parenchymal liver cells and hepatocyte-specific increase in Bcl-xL, associated with signal transducer and activator of transcription 3 (Stat3) phosphorylation. Pre-treatment with ruxolitinib, a selective Janus kinase (JAK) 1/2 inhibitor, prevented the LPS-induced Stat3 phosphorylation and restored the sensitivity of hepatocytes to Fas-mediated apoptosis. Furthermore, ruxolitinib pre-treatment diminished the LPS-induced Bcl-xL up-regulation without an inhibitory effect on LPS-induced expression of pro-inflammatory cytokines. In summary, although the reports are showing that the effects of isolated pro-inflammatory mediators, such as TNF-α or neutrophils, are pro-apoptotic, the overall effect of inflammatory milieu on hepatocytes in vivo is Stat3-dependent desensitization to Fas-mediated apoptosis.
Keywords (english)
Languagecroatian
Publication typeScientific paper - Original scientific paper
Publication statusPublished
Peer reviewPeer review
Publication versionPublished version
Journal titleJournal of Cellular and Molecular Medicine
Numberingvol. 24, no. 5, pp. 2981-2992
p-ISSN1582-1838
e-ISSN1582-4934
DOIhttps://doi.org/10.1111/jcmm.14930
URN:NBNurn:nbn:hr:105:210422
Publication2020-03
Document URLhttps://onlinelibrary.wiley.com/doi/abs/10.1111/jcmm.14930
Type of resourceText
Access conditionsOpen access
Terms of useLicence Attribution 4.0 International (CC BY 4.0) icon
Created on2021-03-23 13:09:29