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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 <jats:italic>Ptpn6<\/jats:italic> deletion (<jats:italic>Ptpn6<\/jats:italic><jats:sup>\n                  <jats:italic>H-KO<\/jats:italic>\n                <\/jats:sup>) were injected with LPS. In contrast to the wild-type mice (<jats:italic>Ptpn6<\/jats:italic><jats:sup>\n                  <jats:italic>f\/f<\/jats:italic>\n                <\/jats:sup>) that started to die by 24\u2009hrs post-inoculation, the <jats:italic>Ptpn6<\/jats:italic><jats:sup>\n                  <jats:italic>H-KO<\/jats:italic>\n                <\/jats:sup> mice exhibited mortality by 6\u2009hrs. In parallel, higher amounts of metabolic markers, pro-inflammatory mediators and circulating cytokines were detected in <jats:italic>Ptpn6<\/jats:italic><jats:sup>\n                  <jats:italic>H-KO<\/jats:italic>\n                <\/jats:sup> mice. Primary Hep obtained from <jats:italic>Ptpn6<\/jats:italic><jats:sup>\n                  <jats:italic>H-KO<\/jats:italic>\n                <\/jats:sup>, also showed increased secretion of pro-inflammatory cytokines and nitric oxide (NO) comparatively to its wild type (<jats:italic>Ptpn6<\/jats:italic><jats:sup>\n                  <jats:italic>f\/f<\/jats:italic>\n                <\/jats:sup>) counterpart. Pharmacological approaches to block TNF-\u03b1 and NO production protected both the <jats:italic>Ptpn6<\/jats:italic><jats:sup>\n                  <jats:italic>f\/f<\/jats:italic>\n                <\/jats:sup> and the <jats:italic>Ptpn6<\/jats:italic><jats:sup>\n                  <jats:italic>H-KO<\/jats:italic>\n                <\/jats:sup> 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.<\/jats:p>","DOI":"10.1038\/s41598-017-02512-7","type":"journal-article","created":{"date-parts":[[2017,5,16]],"date-time":"2017-05-16T08:17:39Z","timestamp":1494922659000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Hepatocyte SHP-1 is a Critical Modulator of Inflammation During Endotoxemia"],"prefix":"10.1038","volume":"7","author":[{"given":"Anupam","family":"Adhikari","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Martel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9","family":"Marette","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Olivier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,5,22]]},"reference":[{"issue":"3","key":"2512_CR1","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1189\/jlb.0912437","volume":"93","author":"M Aziz","year":"2013","unstructured":"Aziz, M., Jacob, A., Yang, W. 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