The Inflammatory Bowel Disease Drug Azathioprine Induces Autophagy via mTORC1 and the Unfolded Protein Response Sensor PERK.
Identifieur interne : 000204 ( Main/Exploration ); précédent : 000203; suivant : 000205The Inflammatory Bowel Disease Drug Azathioprine Induces Autophagy via mTORC1 and the Unfolded Protein Response Sensor PERK.
Auteurs : Kirsty M. Hooper [Royaume-Uni] ; Victor Casanova [Royaume-Uni] ; Sadie Kemp [Royaume-Uni] ; Katherine A. Staines [Royaume-Uni] ; Jack Satsangi [Royaume-Uni] ; Peter G. Barlow [Royaume-Uni] ; Paul Henderson [Royaume-Uni] ; Craig Stevens [Royaume-Uni]Source :
- Inflammatory bowel diseases [ 1536-4844 ] ; 2019.
Descripteurs français
- KwdFr :
- Adolescent (MeSH), Agranulocytes (anatomopathologie), Agranulocytes (effets des médicaments et des substances chimiques), Agranulocytes (métabolisme), Autophagie (MeSH), Azathioprine (pharmacologie), Complexe-1 cible mécanistique de la rapamycine (génétique), Complexe-1 cible mécanistique de la rapamycine (métabolisme), Enfant (MeSH), Escherichia coli (croissance et développement), Escherichia coli (effets des médicaments et des substances chimiques), Femelle (MeSH), Humains (MeSH), Immunosuppresseurs (pharmacologie), Infections à Escherichia coli (microbiologie), Infections à Escherichia coli (métabolisme), Infections à Escherichia coli (traitement médicamenteux), Maladies inflammatoires intestinales (anatomopathologie), Maladies inflammatoires intestinales (métabolisme), Maladies inflammatoires intestinales (traitement médicamenteux), Mâle (MeSH), Réponse aux protéines mal repliées (effets des médicaments et des substances chimiques), eIF-2 Kinase (génétique), eIF-2 Kinase (métabolisme), Études cas-témoins (MeSH).
- MESH :
- anatomopathologie : Agranulocytes, Maladies inflammatoires intestinales.
- croissance et développement : Escherichia coli.
- effets des médicaments et des substances chimiques : Agranulocytes, Escherichia coli, Réponse aux protéines mal repliées.
- génétique : Complexe-1 cible mécanistique de la rapamycine, eIF-2 Kinase.
- microbiologie : Infections à Escherichia coli.
- métabolisme : Agranulocytes, Complexe-1 cible mécanistique de la rapamycine, Infections à Escherichia coli, Maladies inflammatoires intestinales, eIF-2 Kinase.
- pharmacologie : Azathioprine, Immunosuppresseurs.
- traitement médicamenteux : Infections à Escherichia coli, Maladies inflammatoires intestinales.
- Adolescent, Autophagie, Enfant, Femelle, Humains, Mâle, Études cas-témoins.
English descriptors
- KwdEn :
- Adolescent (MeSH), Autophagy (MeSH), Azathioprine (pharmacology), Case-Control Studies (MeSH), Child (MeSH), Escherichia coli (drug effects), Escherichia coli (growth & development), Escherichia coli Infections (drug therapy), Escherichia coli Infections (metabolism), Escherichia coli Infections (microbiology), Female (MeSH), Humans (MeSH), Immunosuppressive Agents (pharmacology), Inflammatory Bowel Diseases (drug therapy), Inflammatory Bowel Diseases (metabolism), Inflammatory Bowel Diseases (pathology), Leukocytes, Mononuclear (drug effects), Leukocytes, Mononuclear (metabolism), Leukocytes, Mononuclear (pathology), Male (MeSH), Mechanistic Target of Rapamycin Complex 1 (genetics), Mechanistic Target of Rapamycin Complex 1 (metabolism), Unfolded Protein Response (drug effects), eIF-2 Kinase (genetics), eIF-2 Kinase (metabolism).
- MESH :
- chemical , genetics : Mechanistic Target of Rapamycin Complex 1, eIF-2 Kinase.
- chemical , metabolism : Mechanistic Target of Rapamycin Complex 1, eIF-2 Kinase.
- chemical , pharmacology : Azathioprine, Immunosuppressive Agents.
- drug effects : Escherichia coli, Leukocytes, Mononuclear, Unfolded Protein Response.
- drug therapy : Escherichia coli Infections, Inflammatory Bowel Diseases.
- growth & development : Escherichia coli.
- metabolism : Escherichia coli Infections, Inflammatory Bowel Diseases, Leukocytes, Mononuclear.
- microbiology : Escherichia coli Infections.
- pathology : Inflammatory Bowel Diseases, Leukocytes, Mononuclear.
- Adolescent, Autophagy, Case-Control Studies, Child, Female, Humans, Male.
Abstract
BACKGROUND
Genetic studies have strongly linked autophagy to Crohn's disease (CD), and stimulating autophagy in CD patients may be therapeutically beneficial. The aim of this study was to evaluate the effect of current inflammatory bowel disease (IBD) drugs on autophagy and investigate molecular mechanisms of action and functional outcomes in relation to this cellular process.
METHODS
Autophagy marker LC3 was evaluated by confocal fluorescence microscopy and flow cytometry. Drug mechanism of action was investigated by polymerase chain reaction (PCR) array with changes in signaling pathways examined by immunoblot and quantitative reverse transcription PCR (RT-qPCR). Clearance of adherent-invasive Escherichia coli (AIEC) and levels of pro-inflammatory cytokine tumor necrosis factor alpha (TNFα) were evaluated by gentamicin protection assays and RT-qPCR, respectively. The marker LC3 was analyzed in peripheral blood mononuclear cells (PBMCs) from pediatric patients by flow cytometry.
RESULTS
Azathioprine induces autophagy via mechanisms involving modulation of mechanistic target of rapamycin (mTORC1) signaling and stimulation of the unfolded protein response (UPR) sensor PERK. Induction of autophagy with azathioprine correlated with the enhanced clearance of AIEC and dampened AIEC-induced increases in TNFα. Azathioprine induced significant increase in autophagosome bound LC3-II in PBMC populations ex vivo, supporting in vitro findings. In patients, the CD-associated ATG16L1 T300A single-nucleotide polymorphism did not attenuate azathioprine induction of autophagy.
CONCLUSIONS
Modulation of autophagy via mTORC1 and the UPR may contribute to the therapeutic efficacy of azathioprine in IBD.
DOI: 10.1093/ibd/izz039
PubMed: 30889246
Affiliations:
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Hooper</name><affiliation wicri:level="2"><nlm:affiliation>School of Applied Sciences, Edinburgh Napier University, Sighthill Campus, Sighthill Court, Edinburgh, Scotland.</nlm:affiliation><country>Royaume-Uni</country><placeName><region type="country">Écosse</region></placeName><wicri:cityArea>School of Applied Sciences, Edinburgh Napier University, Sighthill Campus, Sighthill Court, Edinburgh</wicri:cityArea></affiliation></author><author><name sortKey="Casanova, Victor" sort="Casanova, Victor" uniqKey="Casanova V" first="Victor" last="Casanova">Victor Casanova</name><affiliation wicri:level="2"><nlm:affiliation>School of Applied Sciences, Edinburgh Napier University, Sighthill Campus, Sighthill Court, Edinburgh, Scotland.</nlm:affiliation><country>Royaume-Uni</country><placeName><region type="country">Écosse</region></placeName><wicri:cityArea>School of Applied Sciences, Edinburgh Napier University, Sighthill Campus, Sighthill Court, Edinburgh</wicri:cityArea></affiliation></author><author><name sortKey="Kemp, Sadie" sort="Kemp, Sadie" uniqKey="Kemp S" first="Sadie" last="Kemp">Sadie Kemp</name><affiliation wicri:level="2"><nlm:affiliation>School of Applied Sciences, Edinburgh Napier University, Sighthill Campus, Sighthill Court, Edinburgh, Scotland.</nlm:affiliation><country>Royaume-Uni</country><placeName><region type="country">Écosse</region></placeName><wicri:cityArea>School of Applied Sciences, Edinburgh Napier University, Sighthill Campus, Sighthill Court, Edinburgh</wicri:cityArea></affiliation></author><author><name sortKey="Staines, Katherine A" sort="Staines, Katherine A" uniqKey="Staines K" first="Katherine A" last="Staines">Katherine A. Staines</name><affiliation wicri:level="2"><nlm:affiliation>School of Applied Sciences, Edinburgh Napier University, Sighthill Campus, Sighthill Court, Edinburgh, Scotland.</nlm:affiliation><country>Royaume-Uni</country><placeName><region type="country">Écosse</region></placeName><wicri:cityArea>School of Applied Sciences, Edinburgh Napier University, Sighthill Campus, Sighthill Court, Edinburgh</wicri:cityArea></affiliation></author><author><name sortKey="Satsangi, Jack" sort="Satsangi, Jack" uniqKey="Satsangi J" first="Jack" last="Satsangi">Jack Satsangi</name><affiliation wicri:level="4"><nlm:affiliation>Centre for Genomic & Experimental Medicine, University of Edinburgh, Western General Hospital Campus, Crewe Road, Edinburgh Scotland.</nlm:affiliation><orgName type="university">Université d'Édimbourg</orgName><country>Royaume-Uni</country><placeName><settlement type="city">Édimbourg</settlement><region type="country">Écosse</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Translational Gastroenterology Unit, Nuffield Department of Medicine, John Radcliffe Hospital, Oxford, England.</nlm:affiliation><country>Royaume-Uni</country><placeName><region type="country">Angleterre</region></placeName><wicri:cityArea>Translational Gastroenterology Unit, Nuffield Department of Medicine, John Radcliffe Hospital, Oxford</wicri:cityArea></affiliation></author><author><name sortKey="Barlow, Peter G" sort="Barlow, Peter G" uniqKey="Barlow P" first="Peter G" last="Barlow">Peter G. Barlow</name><affiliation wicri:level="2"><nlm:affiliation>School of Applied Sciences, Edinburgh Napier University, Sighthill Campus, Sighthill Court, Edinburgh, Scotland.</nlm:affiliation><country>Royaume-Uni</country><placeName><region type="country">Écosse</region></placeName><wicri:cityArea>School of Applied Sciences, Edinburgh Napier University, Sighthill Campus, Sighthill Court, Edinburgh</wicri:cityArea></affiliation></author><author><name sortKey="Henderson, Paul" sort="Henderson, Paul" uniqKey="Henderson P" first="Paul" last="Henderson">Paul Henderson</name><affiliation wicri:level="2"><nlm:affiliation>Child Life and Health, University of Edinburgh, Edinburgh, Scotland.</nlm:affiliation><country>Royaume-Uni</country><placeName><region type="country">Écosse</region></placeName><wicri:cityArea>Child Life and Health, University of Edinburgh, Edinburgh</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:affiliation>Department of Pediatric Gastroenterology and Nutrition, Royal Hospital for Sick Children, Edinburgh, Scotland.</nlm:affiliation><country>Royaume-Uni</country><placeName><region type="country">Écosse</region></placeName><wicri:cityArea>Department of Pediatric Gastroenterology and Nutrition, Royal Hospital for Sick Children, Edinburgh</wicri:cityArea></affiliation></author><author><name sortKey="Stevens, Craig" sort="Stevens, Craig" uniqKey="Stevens C" first="Craig" last="Stevens">Craig Stevens</name><affiliation wicri:level="2"><nlm:affiliation>School of Applied Sciences, Edinburgh Napier University, Sighthill Campus, Sighthill Court, Edinburgh, Scotland.</nlm:affiliation><country>Royaume-Uni</country><placeName><region type="country">Écosse</region></placeName><wicri:cityArea>School of Applied Sciences, Edinburgh Napier University, Sighthill Campus, Sighthill Court, Edinburgh</wicri:cityArea></affiliation></author></analytic><series><title level="j">Inflammatory bowel diseases</title><idno type="eISSN">1536-4844</idno><imprint><date when="2019" type="published">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adolescent (MeSH)</term><term>Autophagy (MeSH)</term><term>Azathioprine (pharmacology)</term><term>Case-Control Studies (MeSH)</term><term>Child (MeSH)</term><term>Escherichia coli (drug effects)</term><term>Escherichia coli (growth & development)</term><term>Escherichia coli Infections (drug therapy)</term><term>Escherichia coli Infections (metabolism)</term><term>Escherichia coli Infections (microbiology)</term><term>Female (MeSH)</term><term>Humans (MeSH)</term><term>Immunosuppressive Agents (pharmacology)</term><term>Inflammatory Bowel Diseases (drug therapy)</term><term>Inflammatory Bowel Diseases (metabolism)</term><term>Inflammatory Bowel Diseases (pathology)</term><term>Leukocytes, Mononuclear (drug effects)</term><term>Leukocytes, Mononuclear (metabolism)</term><term>Leukocytes, Mononuclear (pathology)</term><term>Male (MeSH)</term><term>Mechanistic Target of Rapamycin Complex 1 (genetics)</term><term>Mechanistic Target of Rapamycin Complex 1 (metabolism)</term><term>Unfolded Protein Response (drug effects)</term><term>eIF-2 Kinase (genetics)</term><term>eIF-2 Kinase (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Adolescent (MeSH)</term><term>Agranulocytes (anatomopathologie)</term><term>Agranulocytes (effets des médicaments et des substances chimiques)</term><term>Agranulocytes (métabolisme)</term><term>Autophagie (MeSH)</term><term>Azathioprine (pharmacologie)</term><term>Complexe-1 cible mécanistique de la rapamycine (génétique)</term><term>Complexe-1 cible mécanistique de la rapamycine (métabolisme)</term><term>Enfant (MeSH)</term><term>Escherichia coli (croissance et développement)</term><term>Escherichia coli (effets des médicaments et des substances chimiques)</term><term>Femelle (MeSH)</term><term>Humains (MeSH)</term><term>Immunosuppresseurs (pharmacologie)</term><term>Infections à Escherichia coli (microbiologie)</term><term>Infections à Escherichia coli (métabolisme)</term><term>Infections à Escherichia coli (traitement médicamenteux)</term><term>Maladies inflammatoires intestinales (anatomopathologie)</term><term>Maladies inflammatoires intestinales (métabolisme)</term><term>Maladies inflammatoires intestinales (traitement médicamenteux)</term><term>Mâle (MeSH)</term><term>Réponse aux protéines mal repliées (effets des médicaments et des substances chimiques)</term><term>eIF-2 Kinase (génétique)</term><term>eIF-2 Kinase (métabolisme)</term><term>Études cas-témoins (MeSH)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Mechanistic Target of Rapamycin Complex 1</term><term>eIF-2 Kinase</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Mechanistic Target of Rapamycin Complex 1</term><term>eIF-2 Kinase</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Azathioprine</term><term>Immunosuppressive Agents</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Agranulocytes</term><term>Maladies inflammatoires intestinales</term></keywords><keywords scheme="MESH" qualifier="croissance et développement" xml:lang="fr"><term>Escherichia coli</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Escherichia coli</term><term>Leukocytes, Mononuclear</term><term>Unfolded Protein Response</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Escherichia coli Infections</term><term>Inflammatory Bowel Diseases</term></keywords><keywords scheme="MESH" qualifier="effets des médicaments et des substances chimiques" xml:lang="fr"><term>Agranulocytes</term><term>Escherichia coli</term><term>Réponse aux protéines mal repliées</term></keywords><keywords scheme="MESH" qualifier="growth & development" xml:lang="en"><term>Escherichia coli</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Complexe-1 cible mécanistique de la rapamycine</term><term>eIF-2 Kinase</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Escherichia coli Infections</term><term>Inflammatory Bowel Diseases</term><term>Leukocytes, Mononuclear</term></keywords><keywords scheme="MESH" qualifier="microbiologie" xml:lang="fr"><term>Infections à Escherichia coli</term></keywords><keywords scheme="MESH" qualifier="microbiology" xml:lang="en"><term>Escherichia coli Infections</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Agranulocytes</term><term>Complexe-1 cible mécanistique de la rapamycine</term><term>Infections à Escherichia coli</term><term>Maladies inflammatoires intestinales</term><term>eIF-2 Kinase</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Inflammatory Bowel Diseases</term><term>Leukocytes, Mononuclear</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Azathioprine</term><term>Immunosuppresseurs</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Infections à Escherichia coli</term><term>Maladies inflammatoires intestinales</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adolescent</term><term>Autophagy</term><term>Case-Control Studies</term><term>Child</term><term>Female</term><term>Humans</term><term>Male</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adolescent</term><term>Autophagie</term><term>Enfant</term><term>Femelle</term><term>Humains</term><term>Mâle</term><term>Études cas-témoins</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><b>BACKGROUND</b></p><p>Genetic studies have strongly linked autophagy to Crohn's disease (CD), and stimulating autophagy in CD patients may be therapeutically beneficial. The aim of this study was to evaluate the effect of current inflammatory bowel disease (IBD) drugs on autophagy and investigate molecular mechanisms of action and functional outcomes in relation to this cellular process.</p></div><div type="abstract" xml:lang="en"><p><b>METHODS</b></p><p>Autophagy marker LC3 was evaluated by confocal fluorescence microscopy and flow cytometry. Drug mechanism of action was investigated by polymerase chain reaction (PCR) array with changes in signaling pathways examined by immunoblot and quantitative reverse transcription PCR (RT-qPCR). Clearance of adherent-invasive Escherichia coli (AIEC) and levels of pro-inflammatory cytokine tumor necrosis factor alpha (TNFα) were evaluated by gentamicin protection assays and RT-qPCR, respectively. The marker LC3 was analyzed in peripheral blood mononuclear cells (PBMCs) from pediatric patients by flow cytometry.</p></div><div type="abstract" xml:lang="en"><p><b>RESULTS</b></p><p>Azathioprine induces autophagy via mechanisms involving modulation of mechanistic target of rapamycin (mTORC1) signaling and stimulation of the unfolded protein response (UPR) sensor PERK. Induction of autophagy with azathioprine correlated with the enhanced clearance of AIEC and dampened AIEC-induced increases in TNFα. Azathioprine induced significant increase in autophagosome bound LC3-II in PBMC populations ex vivo, supporting in vitro findings. In patients, the CD-associated ATG16L1 T300A single-nucleotide polymorphism did not attenuate azathioprine induction of autophagy.</p></div><div type="abstract" xml:lang="en"><p><b>CONCLUSIONS</b></p><p>Modulation of autophagy via mTORC1 and the UPR may contribute to the therapeutic efficacy of azathioprine in IBD.</p></div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">30889246</PMID><DateCompleted><Year>2020</Year><Month>05</Month><Day>01</Day></DateCompleted><DateRevised><Year>2020</Year><Month>07</Month><Day>15</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1536-4844</ISSN><JournalIssue CitedMedium="Internet"><Volume>25</Volume><Issue>9</Issue><PubDate><Year>2019</Year><Month>08</Month><Day>20</Day></PubDate></JournalIssue><Title>Inflammatory bowel diseases</Title><ISOAbbreviation>Inflamm Bowel Dis</ISOAbbreviation></Journal><ArticleTitle>The Inflammatory Bowel Disease Drug Azathioprine Induces Autophagy via mTORC1 and the Unfolded Protein Response Sensor PERK.</ArticleTitle><Pagination><MedlinePgn>1481-1496</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1093/ibd/izz039</ELocationID><Abstract><AbstractText Label="BACKGROUND">Genetic studies have strongly linked autophagy to Crohn's disease (CD), and stimulating autophagy in CD patients may be therapeutically beneficial. The aim of this study was to evaluate the effect of current inflammatory bowel disease (IBD) drugs on autophagy and investigate molecular mechanisms of action and functional outcomes in relation to this cellular process.</AbstractText><AbstractText Label="METHODS">Autophagy marker LC3 was evaluated by confocal fluorescence microscopy and flow cytometry. Drug mechanism of action was investigated by polymerase chain reaction (PCR) array with changes in signaling pathways examined by immunoblot and quantitative reverse transcription PCR (RT-qPCR). Clearance of adherent-invasive Escherichia coli (AIEC) and levels of pro-inflammatory cytokine tumor necrosis factor alpha (TNFα) were evaluated by gentamicin protection assays and RT-qPCR, respectively. The marker LC3 was analyzed in peripheral blood mononuclear cells (PBMCs) from pediatric patients by flow cytometry.</AbstractText><AbstractText Label="RESULTS">Azathioprine induces autophagy via mechanisms involving modulation of mechanistic target of rapamycin (mTORC1) signaling and stimulation of the unfolded protein response (UPR) sensor PERK. Induction of autophagy with azathioprine correlated with the enhanced clearance of AIEC and dampened AIEC-induced increases in TNFα. Azathioprine induced significant increase in autophagosome bound LC3-II in PBMC populations ex vivo, supporting in vitro findings. In patients, the CD-associated ATG16L1 T300A single-nucleotide polymorphism did not attenuate azathioprine induction of autophagy.</AbstractText><AbstractText Label="CONCLUSIONS">Modulation of autophagy via mTORC1 and the UPR may contribute to the therapeutic efficacy of azathioprine in IBD.</AbstractText><CopyrightInformation>© 2019 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Hooper</LastName><ForeName>Kirsty M</ForeName><Initials>KM</Initials><AffiliationInfo><Affiliation>School of Applied Sciences, Edinburgh Napier University, Sighthill Campus, Sighthill Court, Edinburgh, Scotland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Casanova</LastName><ForeName>Victor</ForeName><Initials>V</Initials><AffiliationInfo><Affiliation>School of Applied Sciences, Edinburgh Napier University, Sighthill Campus, Sighthill Court, Edinburgh, Scotland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kemp</LastName><ForeName>Sadie</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>School of Applied Sciences, Edinburgh Napier University, Sighthill Campus, Sighthill Court, Edinburgh, Scotland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Staines</LastName><ForeName>Katherine A</ForeName><Initials>KA</Initials><AffiliationInfo><Affiliation>School of Applied Sciences, Edinburgh Napier University, Sighthill Campus, Sighthill Court, Edinburgh, Scotland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Satsangi</LastName><ForeName>Jack</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Centre for Genomic & Experimental Medicine, University of Edinburgh, Western General Hospital Campus, Crewe Road, Edinburgh Scotland.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Translational Gastroenterology Unit, Nuffield Department of Medicine, John Radcliffe Hospital, Oxford, England.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Barlow</LastName><ForeName>Peter G</ForeName><Initials>PG</Initials><AffiliationInfo><Affiliation>School of Applied Sciences, Edinburgh Napier University, Sighthill Campus, Sighthill Court, Edinburgh, Scotland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Henderson</LastName><ForeName>Paul</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Child Life and Health, University of Edinburgh, Edinburgh, Scotland.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Pediatric Gastroenterology and Nutrition, Royal Hospital for Sick Children, Edinburgh, Scotland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Stevens</LastName><ForeName>Craig</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>School of Applied Sciences, Edinburgh Napier University, Sighthill Campus, Sighthill Court, Edinburgh, Scotland.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>ETM/389</GrantID><Acronym>CSO_</Acronym><Agency>Chief Scientist Office</Agency><Country>United Kingdom</Country></Grant><Grant><GrantID>G0800759</GrantID><Acronym>MRC_</Acronym><Agency>Medical Research Council</Agency><Country>United Kingdom</Country></Grant><Grant><GrantID>ETM/137</GrantID><Acronym>CSO_</Acronym><Agency>Chief Scientist Office</Agency><Country>United Kingdom</Country></Grant><Grant><GrantID>ETM/395</GrantID><Acronym>CSO_</Acronym><Agency>Chief Scientist Office</Agency><Country>United Kingdom</Country></Grant><Grant><GrantID>G0800675</GrantID><Acronym>MRC_</Acronym><Agency>Medical Research Council</Agency><Country>United Kingdom</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Inflamm Bowel Dis</MedlineTA><NlmUniqueID>9508162</NlmUniqueID><ISSNLinking>1078-0998</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D007166">Immunosuppressive Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.11.1</RegistryNumber><NameOfSubstance UI="C460640">EIF2AK3 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.11.1</RegistryNumber><NameOfSubstance UI="D000076222">Mechanistic Target of Rapamycin Complex 1</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.11.1</RegistryNumber><NameOfSubstance UI="D019892">eIF-2 Kinase</NameOfSubstance></Chemical><Chemical><RegistryNumber>MRK240IY2L</RegistryNumber><NameOfSubstance UI="D001379">Azathioprine</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000293" MajorTopicYN="N">Adolescent</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001343" MajorTopicYN="Y">Autophagy</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001379" MajorTopicYN="N">Azathioprine</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D016022" MajorTopicYN="N">Case-Control Studies</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002648" MajorTopicYN="N">Child</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004926" MajorTopicYN="N">Escherichia coli</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000254" MajorTopicYN="Y">growth & development</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004927" MajorTopicYN="N">Escherichia coli Infections</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="N">drug therapy</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName><QualifierName UI="Q000382" MajorTopicYN="N">microbiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007166" MajorTopicYN="N">Immunosuppressive Agents</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D015212" MajorTopicYN="N">Inflammatory Bowel Diseases</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="N">drug therapy</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName><QualifierName UI="Q000473" MajorTopicYN="Y">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007963" MajorTopicYN="N">Leukocytes, Mononuclear</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000076222" MajorTopicYN="N">Mechanistic Target of Rapamycin Complex 1</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D056811" MajorTopicYN="N">Unfolded Protein Response</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D019892" MajorTopicYN="N">eIF-2 Kinase</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="Y">Azathioprine</Keyword><Keyword MajorTopicYN="Y">adherent-invasive E. coli</Keyword><Keyword MajorTopicYN="Y">autophagy</Keyword><Keyword MajorTopicYN="Y">mTORC1</Keyword><Keyword MajorTopicYN="Y">unfolded protein response</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2018</Year><Month>12</Month><Day>02</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2019</Year><Month>01</Month><Day>26</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2019</Year><Month>02</Month><Day>22</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2019</Year><Month>3</Month><Day>20</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>5</Month><Day>2</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2019</Year><Month>3</Month><Day>20</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">30889246</ArticleId><ArticleId IdType="pii">5393636</ArticleId><ArticleId IdType="doi">10.1093/ibd/izz039</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Royaume-Uni</li></country><region><li>Angleterre</li><li>Écosse</li></region><settlement><li>Édimbourg</li></settlement><orgName><li>Université d'Édimbourg</li></orgName></list><tree><country name="Royaume-Uni"><region name="Écosse"><name sortKey="Hooper, Kirsty M" sort="Hooper, Kirsty M" uniqKey="Hooper K" first="Kirsty M" last="Hooper">Kirsty M. Hooper</name></region><name sortKey="Barlow, Peter G" sort="Barlow, Peter G" uniqKey="Barlow P" first="Peter G" last="Barlow">Peter G. Barlow</name><name sortKey="Casanova, Victor" sort="Casanova, Victor" uniqKey="Casanova V" first="Victor" last="Casanova">Victor Casanova</name><name sortKey="Henderson, Paul" sort="Henderson, Paul" uniqKey="Henderson P" first="Paul" last="Henderson">Paul Henderson</name><name sortKey="Henderson, Paul" sort="Henderson, Paul" uniqKey="Henderson P" first="Paul" last="Henderson">Paul Henderson</name><name sortKey="Kemp, Sadie" sort="Kemp, Sadie" uniqKey="Kemp S" first="Sadie" last="Kemp">Sadie Kemp</name><name sortKey="Satsangi, Jack" sort="Satsangi, Jack" uniqKey="Satsangi J" first="Jack" last="Satsangi">Jack Satsangi</name><name sortKey="Satsangi, Jack" sort="Satsangi, Jack" uniqKey="Satsangi J" first="Jack" last="Satsangi">Jack Satsangi</name><name sortKey="Staines, Katherine A" sort="Staines, Katherine A" uniqKey="Staines K" first="Katherine A" last="Staines">Katherine A. Staines</name><name sortKey="Stevens, Craig" sort="Stevens, Craig" uniqKey="Stevens C" first="Craig" last="Stevens">Craig Stevens</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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|texte= The Inflammatory Bowel Disease Drug Azathioprine Induces Autophagy via mTORC1 and the Unfolded Protein Response Sensor PERK.
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