Macrophage interleukin-6 and tumour necrosis factor-alpha are induced by coronavirus fixation to Toll-like receptor 2/heparan sulphate receptors but not carcinoembryonic cell adhesion antigen 1a.
Identifieur interne : 001F95 ( Ncbi/Checkpoint ); précédent : 001F94; suivant : 001F96Macrophage interleukin-6 and tumour necrosis factor-alpha are induced by coronavirus fixation to Toll-like receptor 2/heparan sulphate receptors but not carcinoembryonic cell adhesion antigen 1a.
Auteurs : Alexandre Jacques [Canada] ; Christian Bleau ; Claire Turbide ; Nicole Beauchemin ; Lucie LamontagneSource :
- Immunology [ 1365-2567 ] ; 2009.
Descripteurs français
- KwdFr :
- Animaux, Antienzymes (pharmacologie), Antigène carcinoembryonnaire (génétique), Antigène carcinoembryonnaire (métabolisme), Butadiènes (pharmacologie), Facteur de nécrose tumorale alpha (agonistes), Facteur de nécrose tumorale alpha (métabolisme), Fibroblastes (), Fibroblastes (métabolisme), Fibroblastes (virologie), Foie (anatomopathologie), Foie (immunologie), Foie (virologie), Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires (immunologie), Héparitine sulfate (immunologie), Héparitine sulfate (métabolisme), Hépatite animale (immunologie), Hépatite animale (virologie), Imidazoles (pharmacologie), Infections à coronavirus (), Interleukine-6 (agonistes), Interleukine-6 (biosynthèse), Lignée cellulaire, Macrophages péritonéaux (), Macrophages péritonéaux (immunologie), Macrophages péritonéaux (virologie), Nitriles (pharmacologie), Protein-Serine-Threonine Kinases (antagonistes et inhibiteurs), Protein-Serine-Threonine Kinases (immunologie), Protein-Serine-Threonine Kinases (métabolisme), Protéines de l'enveloppe virale (immunologie), Pyridines (pharmacologie), Récepteur de type Toll-2 (génétique), Récepteur de type Toll-2 (métabolisme), Réplication virale (immunologie), Souris, Souris knockout, Virus de l'hépatite murine (immunologie), p38 Mitogen-Activated Protein Kinases (antagonistes et inhibiteurs), p38 Mitogen-Activated Protein Kinases (immunologie), p38 Mitogen-Activated Protein Kinases (métabolisme).
- MESH :
- agonistes : Facteur de nécrose tumorale alpha, Interleukine-6.
- anatomopathologie : Foie.
- antagonistes et inhibiteurs : Protein-Serine-Threonine Kinases, p38 Mitogen-Activated Protein Kinases.
- biosynthèse : Interleukine-6.
- génétique : Antigène carcinoembryonnaire, Récepteur de type Toll-2.
- immunologie : Foie, Glycoprotéines membranaires, Héparitine sulfate, Hépatite animale, Macrophages péritonéaux, Protein-Serine-Threonine Kinases, Protéines de l'enveloppe virale, Réplication virale, Virus de l'hépatite murine, p38 Mitogen-Activated Protein Kinases.
- métabolisme : Antigène carcinoembryonnaire, Facteur de nécrose tumorale alpha, Fibroblastes, Héparitine sulfate, Protein-Serine-Threonine Kinases, Récepteur de type Toll-2, p38 Mitogen-Activated Protein Kinases.
- pharmacologie : Antienzymes, Butadiènes, Imidazoles, Nitriles, Pyridines.
- virologie : Fibroblastes, Foie, Hépatite animale, Macrophages péritonéaux.
- Animaux, Fibroblastes, Glycoprotéine de spicule des coronavirus, Infections à coronavirus, Lignée cellulaire, Macrophages péritonéaux, Souris, Souris knockout.
English descriptors
- KwdEn :
- Animals, Butadienes (pharmacology), Carcinoembryonic Antigen (genetics), Carcinoembryonic Antigen (metabolism), Cell Line, Coronavirus Infections (complications), Enzyme Inhibitors (pharmacology), Fibroblasts (drug effects), Fibroblasts (metabolism), Fibroblasts (virology), Heparitin Sulfate (immunology), Heparitin Sulfate (metabolism), Hepatitis, Animal (immunology), Hepatitis, Animal (virology), Imidazoles (pharmacology), Interleukin-6 (agonists), Interleukin-6 (biosynthesis), Liver (immunology), Liver (pathology), Liver (virology), Macrophages, Peritoneal (drug effects), Macrophages, Peritoneal (immunology), Macrophages, Peritoneal (virology), Membrane Glycoproteins (immunology), Mice, Mice, Knockout, Murine hepatitis virus (immunology), Nitriles (pharmacology), Protein-Serine-Threonine Kinases (antagonists & inhibitors), Protein-Serine-Threonine Kinases (immunology), Protein-Serine-Threonine Kinases (metabolism), Pyridines (pharmacology), Spike Glycoprotein, Coronavirus, Toll-Like Receptor 2 (genetics), Toll-Like Receptor 2 (metabolism), Tumor Necrosis Factor-alpha (agonists), Tumor Necrosis Factor-alpha (metabolism), Viral Envelope Proteins (immunology), Virus Replication (immunology), p38 Mitogen-Activated Protein Kinases (antagonists & inhibitors), p38 Mitogen-Activated Protein Kinases (immunology), p38 Mitogen-Activated Protein Kinases (metabolism).
- MESH :
- chemical , agonists : Interleukin-6, Tumor Necrosis Factor-alpha.
- chemical , antagonists & inhibitors : Protein-Serine-Threonine Kinases, p38 Mitogen-Activated Protein Kinases.
- chemical , biosynthesis : Interleukin-6.
- chemical , genetics : Carcinoembryonic Antigen, Toll-Like Receptor 2.
- chemical , immunology : Heparitin Sulfate, Membrane Glycoproteins, Protein-Serine-Threonine Kinases, Viral Envelope Proteins, p38 Mitogen-Activated Protein Kinases.
- chemical , metabolism : Carcinoembryonic Antigen, Heparitin Sulfate, Protein-Serine-Threonine Kinases, Toll-Like Receptor 2, Tumor Necrosis Factor-alpha, p38 Mitogen-Activated Protein Kinases.
- chemical , pharmacology : Butadienes, Enzyme Inhibitors, Imidazoles, Nitriles, Pyridines.
- complications : Coronavirus Infections.
- drug effects : Fibroblasts, Macrophages, Peritoneal.
- immunology : Hepatitis, Animal, Liver, Macrophages, Peritoneal, Murine hepatitis virus, Virus Replication.
- metabolism : Fibroblasts.
- pathology : Liver.
- virology : Fibroblasts, Hepatitis, Animal, Liver, Macrophages, Peritoneal.
- Animals, Cell Line, Mice, Mice, Knockout, Spike Glycoprotein, Coronavirus.
Abstract
A rapid antiviral immune response may be related to viral interaction with the host cell leading to activation of macrophages via pattern recognition receptors (PPRs) or specific viral receptors. Carcinoembryonic cell adhesion antigen 1a (CEACAM1a) is the specific receptor for the mouse hepatitis virus (MHV), a coronavirus known to induce acute viral hepatitis in mice. The objective of this study was to understand the mechanisms responsible for the secretion of high-pathogenic MHV3-induced inflammatory cytokines. We report that the induction of the pro-inflammatory cytokines interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha in peritoneal macrophages does not depend on CEACAM1a, as demonstrated in cells isolated from Ceacam1a(-/-) mice. The induction of IL-6 and TNF-alpha production was related rather to the fixation of the spike (S) protein of MHV3 on Toll-like receptor 2 (TLR2) in regions enriched in heparan sulphate and did not rely on viral replication, as demonstrated with denatured S protein and UV-inactivated virus. High levels of IL-6 and TNF-alpha were produced in livers from infected C57BL/6 mice but not in livers from Tlr2(-/-) mice. The histopathological observations were correlated with the levels of those inflammatory cytokines. Depending on mouse strain, the viral fixation to heparan sulfate/TLR2 stimulated differently the p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-kappaB in the induction of IL-6 and TNF-alpha. These results suggest that TLR2 and heparan sulphate receptors can act as new viral PPRs involved in inflammatory responses.
DOI: 10.1111/j.1365-2567.2008.02946.x
PubMed: 19740307
Affiliations:
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type="published">2009</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Butadienes (pharmacology)</term><term>Carcinoembryonic Antigen (genetics)</term><term>Carcinoembryonic Antigen (metabolism)</term><term>Cell Line</term><term>Coronavirus Infections (complications)</term><term>Enzyme Inhibitors (pharmacology)</term><term>Fibroblasts (drug effects)</term><term>Fibroblasts (metabolism)</term><term>Fibroblasts (virology)</term><term>Heparitin Sulfate (immunology)</term><term>Heparitin Sulfate (metabolism)</term><term>Hepatitis, Animal (immunology)</term><term>Hepatitis, Animal (virology)</term><term>Imidazoles (pharmacology)</term><term>Interleukin-6 (agonists)</term><term>Interleukin-6 (biosynthesis)</term><term>Liver (immunology)</term><term>Liver (pathology)</term><term>Liver (virology)</term><term>Macrophages, Peritoneal (drug effects)</term><term>Macrophages, Peritoneal (immunology)</term><term>Macrophages, Peritoneal (virology)</term><term>Membrane Glycoproteins (immunology)</term><term>Mice</term><term>Mice, Knockout</term><term>Murine hepatitis virus (immunology)</term><term>Nitriles (pharmacology)</term><term>Protein-Serine-Threonine Kinases (antagonists & inhibitors)</term><term>Protein-Serine-Threonine Kinases (immunology)</term><term>Protein-Serine-Threonine Kinases (metabolism)</term><term>Pyridines (pharmacology)</term><term>Spike Glycoprotein, Coronavirus</term><term>Toll-Like Receptor 2 (genetics)</term><term>Toll-Like Receptor 2 (metabolism)</term><term>Tumor Necrosis Factor-alpha (agonists)</term><term>Tumor Necrosis Factor-alpha (metabolism)</term><term>Viral Envelope Proteins (immunology)</term><term>Virus Replication (immunology)</term><term>p38 Mitogen-Activated Protein Kinases (antagonists & inhibitors)</term><term>p38 Mitogen-Activated Protein Kinases (immunology)</term><term>p38 Mitogen-Activated Protein Kinases (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Antienzymes (pharmacologie)</term><term>Antigène carcinoembryonnaire (génétique)</term><term>Antigène carcinoembryonnaire (métabolisme)</term><term>Butadiènes (pharmacologie)</term><term>Facteur de nécrose tumorale alpha (agonistes)</term><term>Facteur de nécrose tumorale alpha (métabolisme)</term><term>Fibroblastes ()</term><term>Fibroblastes (métabolisme)</term><term>Fibroblastes (virologie)</term><term>Foie (anatomopathologie)</term><term>Foie (immunologie)</term><term>Foie (virologie)</term><term>Glycoprotéine de spicule des coronavirus</term><term>Glycoprotéines membranaires (immunologie)</term><term>Héparitine sulfate (immunologie)</term><term>Héparitine sulfate (métabolisme)</term><term>Hépatite animale (immunologie)</term><term>Hépatite animale (virologie)</term><term>Imidazoles (pharmacologie)</term><term>Infections à coronavirus ()</term><term>Interleukine-6 (agonistes)</term><term>Interleukine-6 (biosynthèse)</term><term>Lignée cellulaire</term><term>Macrophages péritonéaux ()</term><term>Macrophages péritonéaux (immunologie)</term><term>Macrophages péritonéaux (virologie)</term><term>Nitriles (pharmacologie)</term><term>Protein-Serine-Threonine Kinases (antagonistes et inhibiteurs)</term><term>Protein-Serine-Threonine Kinases (immunologie)</term><term>Protein-Serine-Threonine Kinases (métabolisme)</term><term>Protéines de l'enveloppe virale (immunologie)</term><term>Pyridines (pharmacologie)</term><term>Récepteur de type Toll-2 (génétique)</term><term>Récepteur de type Toll-2 (métabolisme)</term><term>Réplication virale (immunologie)</term><term>Souris</term><term>Souris knockout</term><term>Virus de l'hépatite murine (immunologie)</term><term>p38 Mitogen-Activated Protein Kinases (antagonistes et inhibiteurs)</term><term>p38 Mitogen-Activated Protein Kinases (immunologie)</term><term>p38 Mitogen-Activated Protein Kinases (métabolisme)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="agonists" xml:lang="en"><term>Interleukin-6</term><term>Tumor Necrosis Factor-alpha</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Protein-Serine-Threonine Kinases</term><term>p38 Mitogen-Activated Protein Kinases</term></keywords><keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Interleukin-6</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Carcinoembryonic Antigen</term><term>Toll-Like Receptor 2</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Heparitin Sulfate</term><term>Membrane Glycoproteins</term><term>Protein-Serine-Threonine Kinases</term><term>Viral Envelope Proteins</term><term>p38 Mitogen-Activated Protein Kinases</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Carcinoembryonic Antigen</term><term>Heparitin Sulfate</term><term>Protein-Serine-Threonine Kinases</term><term>Toll-Like Receptor 2</term><term>Tumor Necrosis Factor-alpha</term><term>p38 Mitogen-Activated Protein Kinases</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Butadienes</term><term>Enzyme Inhibitors</term><term>Imidazoles</term><term>Nitriles</term><term>Pyridines</term></keywords><keywords scheme="MESH" qualifier="agonistes" xml:lang="fr"><term>Facteur de nécrose tumorale alpha</term><term>Interleukine-6</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Foie</term></keywords><keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Protein-Serine-Threonine Kinases</term><term>p38 Mitogen-Activated Protein Kinases</term></keywords><keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr"><term>Interleukine-6</term></keywords><keywords scheme="MESH" qualifier="complications" xml:lang="en"><term>Coronavirus Infections</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Fibroblasts</term><term>Macrophages, Peritoneal</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Antigène carcinoembryonnaire</term><term>Récepteur de type Toll-2</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Foie</term><term>Glycoprotéines membranaires</term><term>Héparitine sulfate</term><term>Hépatite animale</term><term>Macrophages péritonéaux</term><term>Protein-Serine-Threonine Kinases</term><term>Protéines de l'enveloppe virale</term><term>Réplication virale</term><term>Virus de l'hépatite murine</term><term>p38 Mitogen-Activated Protein Kinases</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Hepatitis, Animal</term><term>Liver</term><term>Macrophages, Peritoneal</term><term>Murine hepatitis virus</term><term>Virus Replication</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Fibroblasts</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Antigène carcinoembryonnaire</term><term>Facteur de nécrose tumorale alpha</term><term>Fibroblastes</term><term>Héparitine sulfate</term><term>Protein-Serine-Threonine Kinases</term><term>Récepteur de type Toll-2</term><term>p38 Mitogen-Activated Protein Kinases</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Liver</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Antienzymes</term><term>Butadiènes</term><term>Imidazoles</term><term>Nitriles</term><term>Pyridines</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Fibroblastes</term><term>Foie</term><term>Hépatite animale</term><term>Macrophages péritonéaux</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Fibroblasts</term><term>Hepatitis, Animal</term><term>Liver</term><term>Macrophages, Peritoneal</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cell Line</term><term>Mice</term><term>Mice, Knockout</term><term>Spike Glycoprotein, Coronavirus</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Fibroblastes</term><term>Glycoprotéine de spicule des coronavirus</term><term>Infections à coronavirus</term><term>Lignée cellulaire</term><term>Macrophages péritonéaux</term><term>Souris</term><term>Souris knockout</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">A rapid antiviral immune response may be related to viral interaction with the host cell leading to activation of macrophages via pattern recognition receptors (PPRs) or specific viral receptors. Carcinoembryonic cell adhesion antigen 1a (CEACAM1a) is the specific receptor for the mouse hepatitis virus (MHV), a coronavirus known to induce acute viral hepatitis in mice. The objective of this study was to understand the mechanisms responsible for the secretion of high-pathogenic MHV3-induced inflammatory cytokines. We report that the induction of the pro-inflammatory cytokines interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha in peritoneal macrophages does not depend on CEACAM1a, as demonstrated in cells isolated from Ceacam1a(-/-) mice. The induction of IL-6 and TNF-alpha production was related rather to the fixation of the spike (S) protein of MHV3 on Toll-like receptor 2 (TLR2) in regions enriched in heparan sulphate and did not rely on viral replication, as demonstrated with denatured S protein and UV-inactivated virus. High levels of IL-6 and TNF-alpha were produced in livers from infected C57BL/6 mice but not in livers from Tlr2(-/-) mice. The histopathological observations were correlated with the levels of those inflammatory cytokines. Depending on mouse strain, the viral fixation to heparan sulfate/TLR2 stimulated differently the p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-kappaB in the induction of IL-6 and TNF-alpha. These results suggest that TLR2 and heparan sulphate receptors can act as new viral PPRs involved in inflammatory responses.</div></front></TEI><affiliations><list><country><li>Canada</li></country><region><li>Québec</li></region><settlement><li>Montréal</li></settlement><orgName><li>Université du Québec à Montréal</li></orgName></list><tree><noCountry><name sortKey="Beauchemin, Nicole" sort="Beauchemin, Nicole" uniqKey="Beauchemin N" first="Nicole" last="Beauchemin">Nicole Beauchemin</name><name sortKey="Bleau, Christian" sort="Bleau, Christian" uniqKey="Bleau C" first="Christian" last="Bleau">Christian Bleau</name><name sortKey="Lamontagne, Lucie" sort="Lamontagne, Lucie" uniqKey="Lamontagne L" first="Lucie" last="Lamontagne">Lucie Lamontagne</name><name sortKey="Turbide, Claire" sort="Turbide, Claire" uniqKey="Turbide C" first="Claire" last="Turbide">Claire Turbide</name></noCountry><country name="Canada"><region name="Québec"><name sortKey="Jacques, Alexandre" sort="Jacques, Alexandre" uniqKey="Jacques A" first="Alexandre" last="Jacques">Alexandre Jacques</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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