Hepatocyte SHP-1 is a Critical Modulator of Inflammation During Endotoxemia

Abstract Liver hepatocytes (Hep) are known to be central players during the inflammatory response to systemic infection. Interestingly, the protein tyrosine phosphatases (PTP) SHP-1, has been recognized as a major regulator of inflammation; however their implication in the control of Hep-mediated in...

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Autores principales:	Anupam Adhikari, Caroline Martel, André Marette, Martin Olivier
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f0f64b4bc663496380bc031511babb6f
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spelling	oai:doaj.org-article:f0f64b4bc663496380bc031511babb6f2021-12-02T11:41:20ZHepatocyte SHP-1 is a Critical Modulator of Inflammation During Endotoxemia10.1038/s41598-017-02512-72045-2322https://doaj.org/article/f0f64b4bc663496380bc031511babb6f2017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02512-7https://doaj.org/toc/2045-2322Abstract Liver hepatocytes (Hep) are known to be central players during the inflammatory response to systemic infection. Interestingly, the protein tyrosine phosphatases (PTP) SHP-1, has been recognized as a major regulator of inflammation; however their implication in the control of Hep-mediated inflammatory response is still unknown. To study its implication in the regulation of the Hep-mediated inflammatory response during endotoxemia, Cre-Lox mice with a Hep-specific Ptpn6 deletion (Ptpn6 H-KO ) were injected with LPS. In contrast to the wild-type mice (Ptpn6 f/f ) that started to die by 24 hrs post-inoculation, the Ptpn6 H-KO mice exhibited mortality by 6 hrs. In parallel, higher amounts of metabolic markers, pro-inflammatory mediators and circulating cytokines were detected in Ptpn6 H-KO mice. Primary Hep obtained from Ptpn6 H-KO , also showed increased secretion of pro-inflammatory cytokines and nitric oxide (NO) comparatively to its wild type (Ptpn6 f/f ) counterpart. Pharmacological approaches to block TNF-α and NO production protected both the Ptpn6 f/f and the Ptpn6 H-KO mice against deadly LPS-mediated endotoxemia. Collectively, these results establish hepatocyte SHP-1 is a critical player regulating systemic inflammation. Our findings further suggest that SHP-1 activation could represent a new therapeutic avenue to better control inflammatory-related pathologies.Anupam AdhikariCaroline MartelAndré MaretteMartin OlivierNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Anupam Adhikari Caroline Martel André Marette Martin Olivier Hepatocyte SHP-1 is a Critical Modulator of Inflammation During Endotoxemia
description	Abstract Liver hepatocytes (Hep) are known to be central players during the inflammatory response to systemic infection. Interestingly, the protein tyrosine phosphatases (PTP) SHP-1, has been recognized as a major regulator of inflammation; however their implication in the control of Hep-mediated inflammatory response is still unknown. To study its implication in the regulation of the Hep-mediated inflammatory response during endotoxemia, Cre-Lox mice with a Hep-specific Ptpn6 deletion (Ptpn6 H-KO ) were injected with LPS. In contrast to the wild-type mice (Ptpn6 f/f ) that started to die by 24 hrs post-inoculation, the Ptpn6 H-KO mice exhibited mortality by 6 hrs. In parallel, higher amounts of metabolic markers, pro-inflammatory mediators and circulating cytokines were detected in Ptpn6 H-KO mice. Primary Hep obtained from Ptpn6 H-KO , also showed increased secretion of pro-inflammatory cytokines and nitric oxide (NO) comparatively to its wild type (Ptpn6 f/f ) counterpart. Pharmacological approaches to block TNF-α and NO production protected both the Ptpn6 f/f and the Ptpn6 H-KO mice against deadly LPS-mediated endotoxemia. Collectively, these results establish hepatocyte SHP-1 is a critical player regulating systemic inflammation. Our findings further suggest that SHP-1 activation could represent a new therapeutic avenue to better control inflammatory-related pathologies.
format	article
author	Anupam Adhikari Caroline Martel André Marette Martin Olivier
author_facet	Anupam Adhikari Caroline Martel André Marette Martin Olivier
author_sort	Anupam Adhikari
title	Hepatocyte SHP-1 is a Critical Modulator of Inflammation During Endotoxemia
title_short	Hepatocyte SHP-1 is a Critical Modulator of Inflammation During Endotoxemia
title_full	Hepatocyte SHP-1 is a Critical Modulator of Inflammation During Endotoxemia
title_fullStr	Hepatocyte SHP-1 is a Critical Modulator of Inflammation During Endotoxemia
title_full_unstemmed	Hepatocyte SHP-1 is a Critical Modulator of Inflammation During Endotoxemia
title_sort	hepatocyte shp-1 is a critical modulator of inflammation during endotoxemia
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/f0f64b4bc663496380bc031511babb6f
work_keys_str_mv	AT anupamadhikari hepatocyteshp1isacriticalmodulatorofinflammationduringendotoxemia AT carolinemartel hepatocyteshp1isacriticalmodulatorofinflammationduringendotoxemia AT andremarette hepatocyteshp1isacriticalmodulatorofinflammationduringendotoxemia AT martinolivier hepatocyteshp1isacriticalmodulatorofinflammationduringendotoxemia
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Hepatocyte SHP-1 is a Critical Modulator of Inflammation During Endotoxemia

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