AUTOTAXIN DOWNREGULATES LPS – INDUCED MICROGLIA ACTIVATION AND PRO-INFLAMMATORY CYTOKINES PRODUCTION
Identifieur interne : 000A66 ( Main/Exploration ); précédent : 000A65; suivant : 000A67AUTOTAXIN DOWNREGULATES LPS – INDUCED MICROGLIA ACTIVATION AND PRO-INFLAMMATORY CYTOKINES PRODUCTION
Auteurs : Rana Awada [France] ; Jean Sébastien Saulnier-Blache [France] ; Sandra Grès [France] ; Emmanuel Bourdon [France] ; Philippe Rondeau [France] ; Avinash Parimisetty [France] ; Ruben Orihuela [États-Unis] ; G. Jean Harry [États-Unis] ; Christian Lefebvre D Ellencourt [France]Source :
- Journal of cellular biochemistry [ 0730-2312 ] ; 2014.
Abstract
Inflammation is essential in defense against infection or injury. It is tightly regulated, as over-response can be detrimental, especially in immune-privileged organs such as the central nervous system (CNS). Microglia constitutes the major source of inflammatory factors, but are also involved in the regulation of the inflammation and in the reparation. Autotaxin (ATX), a phospholipase D, converts lysophosphatidylcholine into lysophosphatidic acid (LPA) and is upregulated in several CNS injuries. LPA, a pleiotropic immunomodulatory factor, can induce multiple cellular processes including morphological changes, proliferation, death and survival.
We investigated ATX effects on microglia inflammatory response to lipopolysaccharide (LPS), mimicking gram-negative infection. Murine BV-2 microglia and stable transfected, overexpressing ATX-BV-2 (A+) microglia were treated with LPS. Tumor necrosis factor α (TNFα), interleukin (IL)-6 and IL-10 mRNA and proteins levels were examined by qRT-PCR and ELISA, respectively. Secreted LPA was quantified by a radioenzymatic assay and microglial activation markers (CD11b, CD14, B7.1 and B7.2) were determined by flow cytometry.
ATX expression and LPA production were significantly enhanced in LPS treated BV-2 cells. LPS induction of mRNA and protein level for TNFα and IL-6 were inhibited in A+ cells, while IL-10 was increased. CD11b, CD14, and B7.1 and B7.2 expressions were reduced in A+ cells.
Our results strongly suggest deactivation of microglia and an IL-10 inhibitory of ATX with LPS induced microglia activation.
Url:
DOI: 10.1002/jcb.24889
PubMed: 25053164
PubMed Central: 4275303
Affiliations:
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Cassin, CS 92003, 97715, Saint Denis Cedex and Plateforme CYROI, 2 Rue Maxime Rivière, BP 80 005, 97491 Sainte Clotilde Cedex, Reunion Island, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Groupe d’Etude sur l’Inflammation Chronique et l’Obésité (GEICO) EA 4516, Université de La Réunion, 15 avenue R. Cassin, CS 92003, 97715, Saint Denis Cedex and Plateforme CYROI, 2 Rue Maxime Rivière, BP 80 005, 97491 Sainte Clotilde Cedex, Reunion Island</wicri:regionArea><wicri:noRegion>Reunion Island</wicri:noRegion><wicri:noRegion>Reunion Island</wicri:noRegion></affiliation></author><author><name sortKey="Saulnier Blache, Jean Sebastien" sort="Saulnier Blache, Jean Sebastien" uniqKey="Saulnier Blache J" first="Jean Sébastien" last="Saulnier-Blache">Jean Sébastien Saulnier-Blache</name><affiliation wicri:level="1"><nlm:aff id="A2">INSERM U1048, Institut des maladies métaboliques et cardiovasculaires (I2MC). 1 avenue Jean Poulhès, BP84225, 31432 Toulouse, Cedex 4, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM U1048, Institut des maladies métaboliques et cardiovasculaires (I2MC). 1 avenue Jean Poulhès, BP84225, 31432 Toulouse, Cedex 4</wicri:regionArea><wicri:noRegion>Cedex 4</wicri:noRegion><wicri:noRegion>Cedex 4</wicri:noRegion></affiliation></author><author><name sortKey="Gres, Sandra" sort="Gres, Sandra" uniqKey="Gres S" first="Sandra" last="Grès">Sandra Grès</name><affiliation wicri:level="1"><nlm:aff id="A2">INSERM U1048, Institut des maladies métaboliques et cardiovasculaires (I2MC). 1 avenue Jean Poulhès, BP84225, 31432 Toulouse, Cedex 4, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM U1048, Institut des maladies métaboliques et cardiovasculaires (I2MC). 1 avenue Jean Poulhès, BP84225, 31432 Toulouse, Cedex 4</wicri:regionArea><wicri:noRegion>Cedex 4</wicri:noRegion><wicri:noRegion>Cedex 4</wicri:noRegion></affiliation></author><author><name sortKey="Bourdon, Emmanuel" sort="Bourdon, Emmanuel" uniqKey="Bourdon E" first="Emmanuel" last="Bourdon">Emmanuel Bourdon</name><affiliation wicri:level="1"><nlm:aff id="A1">Groupe d’Etude sur l’Inflammation Chronique et l’Obésité (GEICO) EA 4516, Université de La Réunion, 15 avenue R. Cassin, CS 92003, 97715, Saint Denis Cedex and Plateforme CYROI, 2 Rue Maxime Rivière, BP 80 005, 97491 Sainte Clotilde Cedex, Reunion Island, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Groupe d’Etude sur l’Inflammation Chronique et l’Obésité (GEICO) EA 4516, Université de La Réunion, 15 avenue R. Cassin, CS 92003, 97715, Saint Denis Cedex and Plateforme CYROI, 2 Rue Maxime Rivière, BP 80 005, 97491 Sainte Clotilde Cedex, Reunion Island</wicri:regionArea><wicri:noRegion>Reunion Island</wicri:noRegion><wicri:noRegion>Reunion Island</wicri:noRegion></affiliation></author><author><name sortKey="Rondeau, Philippe" sort="Rondeau, Philippe" uniqKey="Rondeau P" first="Philippe" last="Rondeau">Philippe Rondeau</name><affiliation wicri:level="1"><nlm:aff id="A1">Groupe d’Etude sur l’Inflammation Chronique et l’Obésité (GEICO) EA 4516, Université de La Réunion, 15 avenue R. Cassin, CS 92003, 97715, Saint Denis Cedex and Plateforme CYROI, 2 Rue Maxime Rivière, BP 80 005, 97491 Sainte Clotilde Cedex, Reunion Island, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Groupe d’Etude sur l’Inflammation Chronique et l’Obésité (GEICO) EA 4516, Université de La Réunion, 15 avenue R. Cassin, CS 92003, 97715, Saint Denis Cedex and Plateforme CYROI, 2 Rue Maxime Rivière, BP 80 005, 97491 Sainte Clotilde Cedex, Reunion Island</wicri:regionArea><wicri:noRegion>Reunion Island</wicri:noRegion><wicri:noRegion>Reunion Island</wicri:noRegion></affiliation></author><author><name sortKey="Parimisetty, Avinash" sort="Parimisetty, Avinash" uniqKey="Parimisetty A" first="Avinash" last="Parimisetty">Avinash Parimisetty</name><affiliation wicri:level="1"><nlm:aff id="A1">Groupe d’Etude sur l’Inflammation Chronique et l’Obésité (GEICO) EA 4516, Université de La Réunion, 15 avenue R. Cassin, CS 92003, 97715, Saint Denis Cedex and Plateforme CYROI, 2 Rue Maxime Rivière, BP 80 005, 97491 Sainte Clotilde Cedex, Reunion Island, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Groupe d’Etude sur l’Inflammation Chronique et l’Obésité (GEICO) EA 4516, Université de La Réunion, 15 avenue R. Cassin, CS 92003, 97715, Saint Denis Cedex and Plateforme CYROI, 2 Rue Maxime Rivière, BP 80 005, 97491 Sainte Clotilde Cedex, Reunion Island</wicri:regionArea><wicri:noRegion>Reunion Island</wicri:noRegion><wicri:noRegion>Reunion Island</wicri:noRegion></affiliation></author><author><name sortKey="Orihuela, Ruben" sort="Orihuela, Ruben" uniqKey="Orihuela R" first="Ruben" last="Orihuela">Ruben Orihuela</name><affiliation wicri:level="2"><nlm:aff id="A3">Neurotoxicology Group, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health, Dept. of Health and Human Services, Research Triangle Park, North Carolina, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Neurotoxicology Group, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health, Dept. of Health and Human Services, Research Triangle Park, North Carolina</wicri:regionArea><placeName><region type="state">Caroline du Nord</region></placeName></affiliation></author><author><name sortKey="Harry, G Jean" sort="Harry, G Jean" uniqKey="Harry G" first="G. Jean" last="Harry">G. Jean Harry</name><affiliation wicri:level="2"><nlm:aff id="A3">Neurotoxicology Group, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health, Dept. of Health and Human Services, Research Triangle Park, North Carolina, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Neurotoxicology Group, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health, Dept. of Health and Human Services, Research Triangle Park, North Carolina</wicri:regionArea><placeName><region type="state">Caroline du Nord</region></placeName></affiliation></author><author><name sortKey="D Ellencourt, Christian Lefebvre" sort="D Ellencourt, Christian Lefebvre" uniqKey="D Ellencourt C" first="Christian Lefebvre" last="D Ellencourt">Christian Lefebvre D Ellencourt</name><affiliation wicri:level="1"><nlm:aff id="A1">Groupe d’Etude sur l’Inflammation Chronique et l’Obésité (GEICO) EA 4516, Université de La Réunion, 15 avenue R. Cassin, CS 92003, 97715, Saint Denis Cedex and Plateforme CYROI, 2 Rue Maxime Rivière, BP 80 005, 97491 Sainte Clotilde Cedex, Reunion Island, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Groupe d’Etude sur l’Inflammation Chronique et l’Obésité (GEICO) EA 4516, Université de La Réunion, 15 avenue R. Cassin, CS 92003, 97715, Saint Denis Cedex and Plateforme CYROI, 2 Rue Maxime Rivière, BP 80 005, 97491 Sainte Clotilde Cedex, Reunion Island</wicri:regionArea><wicri:noRegion>Reunion Island</wicri:noRegion><wicri:noRegion>Reunion Island</wicri:noRegion></affiliation></author></analytic><series><title level="j">Journal of cellular biochemistry</title><idno type="ISSN">0730-2312</idno><idno type="eISSN">1097-4644</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P1">Inflammation is essential in defense against infection or injury. It is tightly regulated, as over-response can be detrimental, especially in immune-privileged organs such as the central nervous system (CNS). Microglia constitutes the major source of inflammatory factors, but are also involved in the regulation of the inflammation and in the reparation. Autotaxin (ATX), a phospholipase D, converts lysophosphatidylcholine into lysophosphatidic acid (LPA) and is upregulated in several CNS injuries. LPA, a pleiotropic immunomodulatory factor, can induce multiple cellular processes including morphological changes, proliferation, death and survival.</p><p id="P2">We investigated ATX effects on microglia inflammatory response to lipopolysaccharide (LPS), mimicking gram-negative infection. Murine BV-2 microglia and stable transfected, overexpressing ATX-BV-2 (A+) microglia were treated with LPS. Tumor necrosis factor α (TNFα), interleukin (IL)-6 and IL-10 mRNA and proteins levels were examined by qRT-PCR and ELISA, respectively. Secreted LPA was quantified by a radioenzymatic assay and microglial activation markers (CD11b, CD14, B7.1 and B7.2) were determined by flow cytometry.</p><p id="P3">ATX expression and LPA production were significantly enhanced in LPS treated BV-2 cells. LPS induction of mRNA and protein level for TNFα and IL-6 were inhibited in A+ cells, while IL-10 was increased. CD11b, CD14, and B7.1 and B7.2 expressions were reduced in A+ cells.</p><p id="P4">Our results strongly suggest deactivation of microglia and an IL-10 inhibitory of ATX with LPS induced microglia activation.</p></div></front></TEI><affiliations><list><country><li>France</li><li>États-Unis</li></country><region><li>Caroline du Nord</li></region></list><tree><country name="France"><noRegion><name sortKey="Awada, Rana" sort="Awada, Rana" uniqKey="Awada R" first="Rana" last="Awada">Rana Awada</name></noRegion><name sortKey="Bourdon, Emmanuel" sort="Bourdon, Emmanuel" uniqKey="Bourdon E" first="Emmanuel" last="Bourdon">Emmanuel Bourdon</name><name sortKey="D Ellencourt, Christian Lefebvre" sort="D Ellencourt, Christian Lefebvre" uniqKey="D Ellencourt C" first="Christian Lefebvre" last="D Ellencourt">Christian Lefebvre D Ellencourt</name><name sortKey="Gres, Sandra" sort="Gres, Sandra" uniqKey="Gres S" first="Sandra" last="Grès">Sandra Grès</name><name sortKey="Parimisetty, Avinash" sort="Parimisetty, Avinash" uniqKey="Parimisetty A" first="Avinash" last="Parimisetty">Avinash Parimisetty</name><name sortKey="Rondeau, Philippe" sort="Rondeau, Philippe" uniqKey="Rondeau P" first="Philippe" last="Rondeau">Philippe Rondeau</name><name sortKey="Saulnier Blache, Jean Sebastien" sort="Saulnier Blache, Jean Sebastien" uniqKey="Saulnier Blache J" first="Jean Sébastien" last="Saulnier-Blache">Jean Sébastien Saulnier-Blache</name></country><country name="États-Unis"><region name="Caroline du Nord"><name sortKey="Orihuela, Ruben" sort="Orihuela, Ruben" uniqKey="Orihuela R" first="Ruben" last="Orihuela">Ruben Orihuela</name></region><name sortKey="Harry, G Jean" sort="Harry, G Jean" uniqKey="Harry G" first="G. Jean" last="Harry">G. Jean Harry</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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