Potent repression of C-reactive protein (CRP) expression by the JAK1/2 inhibitor ruxolitinib in inflammatory human hepatocytes.
Identifieur interne : 000251 ( PubMed/Curation ); précédent : 000250; suivant : 000252Potent repression of C-reactive protein (CRP) expression by the JAK1/2 inhibitor ruxolitinib in inflammatory human hepatocytes.
Auteurs : Marie Febvre-James [France] ; Valérie Lecureur [France] ; Olivier Fardel [France]Source :
- Inflammation research : official journal of the European Histamine Research Society ... [et al.] [ 1420-908X ] ; 2020.
Abstract
To determine whether inflammatory hepatocytes may constitute primary targets for ruxolitinib, a Janus kinase (JAK) inhibitor, its effects towards expression of hepatic acute-phase proteins, especially C-reactive protein (CRP), were assessed.
DOI: 10.1007/s00011-019-01293-1
PubMed: 31654094
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[et al.]</title><idno type="eISSN">1420-908X</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">To determine whether inflammatory hepatocytes may constitute primary targets for ruxolitinib, a Janus kinase (JAK) inhibitor, its effects towards expression of hepatic acute-phase proteins, especially C-reactive protein (CRP), were assessed.</div></front></TEI><pubmed><MedlineCitation Status="In-Process" Owner="NLM"><PMID Version="1">31654094</PMID><DateRevised><Year>2020</Year><Month>02</Month><Day>26</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1420-908X</ISSN><JournalIssue CitedMedium="Internet"><Volume>69</Volume><Issue>1</Issue><PubDate><Year>2020</Year><Month>Jan</Month></PubDate></JournalIssue><Title>Inflammation research : official journal of the European Histamine Research Society ... [et al.]</Title><ISOAbbreviation>Inflamm. Res.</ISOAbbreviation></Journal><ArticleTitle>Potent repression of C-reactive protein (CRP) expression by the JAK1/2 inhibitor ruxolitinib in inflammatory human hepatocytes.</ArticleTitle><Pagination><MedlinePgn>51-62</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1007/s00011-019-01293-1</ELocationID><Abstract><AbstractText Label="OBJECTIVE AND DESIGN" NlmCategory="OBJECTIVE">To determine whether inflammatory hepatocytes may constitute primary targets for ruxolitinib, a Janus kinase (JAK) inhibitor, its effects towards expression of hepatic acute-phase proteins, especially C-reactive protein (CRP), were assessed.</AbstractText><AbstractText Label="MATERIALS" NlmCategory="METHODS">Ruxolitinib effects were analysed in primary human hepatocytes and human hepatoma HepaRG cells exposed to various inflammatory stimuli.</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">Ruxolitinib was found to fully inhibit lipopolysaccharide (LPS)-induced CRP secretion and mRNA expression, at concentrations (IC<sub>50</sub> = 12.9 nM) achievable in human blood. It similarly repressed CRP up-regulation due to several Toll-like receptor agonists or pro-inflammatory cytokines [interleukin (IL) 1β, IL6 and tumour necrosis factor α] and counteracted LPS-mediated induction of serum amyloid A, fibrinogen, haptoglobin and serpin. Ruxolitinib was additionally found to block the activation of the IL6/JAK/signal transducer and activator of transcription (STAT) pathway triggered by LPS and whose inhibition by the neutralizing anti-IL6 receptor antibody tocilizumab prevented CRP induction.</AbstractText><AbstractText Label="CONCLUSION" NlmCategory="CONCLUSIONS">Ruxolitinib can potently repress induction of CRP in inflammatory human hepatocytes, most likely through targeting the IL6/JAK/STAT signalling cascade. Hepatic production of acute-phase proteins during liver inflammation may, therefore, constitute a target for ruxolitinib.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Febvre-James</LastName><ForeName>Marie</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail)-UMR_S 1085, 35000, Rennes, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lecureur</LastName><ForeName>Valérie</ForeName><Initials>V</Initials><AffiliationInfo><Affiliation>Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail)-UMR_S 1085, 35000, Rennes, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fardel</LastName><ForeName>Olivier</ForeName><Initials>O</Initials><Identifier Source="ORCID">http://orcid.org/0000-0001-5657-4255</Identifier><AffiliationInfo><Affiliation>Univ Rennes, Inserm, CHU Rennes, EHESP, Irset (Institut de recherche en santé, environnement et travail)-UMR_S 1085, Campus Santé, 2 Avenue du Pr Léon Bernard, 35043, Rennes, France. olivier.fardel@univ-rennes1.fr.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2019</Year><Month>10</Month><Day>25</Day></ArticleDate></Article><MedlineJournalInfo><Country>Switzerland</Country><MedlineTA>Inflamm Res</MedlineTA><NlmUniqueID>9508160</NlmUniqueID><ISSNLinking>1023-3830</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">C-reactive protein</Keyword><Keyword MajorTopicYN="N">Hepatic inflammation</Keyword><Keyword MajorTopicYN="N">Interleukin 6</Keyword><Keyword MajorTopicYN="N">JAK inhibition</Keyword><Keyword 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