Ibudilast suppresses TNFα production by glial cells functioning mainly as type III phosphodiesterase inhibitor in the CNS
Identifieur interne : 001945 ( Main/Exploration ); précédent : 001944; suivant : 001946Ibudilast suppresses TNFα production by glial cells functioning mainly as type III phosphodiesterase inhibitor in the CNS
Auteurs : Akio Suzumura [Japon] ; Atsushi Ito [Japon] ; Minka Yoshikawa [Japon] ; Makoto Sawada [Japon]Source :
- Brain Research [ 0006-8993 ] ; 1999.
English descriptors
- KwdEn :
- Teeft :
- Antigen expression, Antisense, Assay, Astrocyte, Brain research, Cell death, Cyclic, Cytokine, Cytokine production, Demyelination, Dipyridamole, Glial, Glial cells, Higher concentrations, Ibudilast, Immunol, Inflammatory demyelination, Inhibitor, Inhibitory activity, Inhibitory effects, Microglia, Mrna, Multiple sclerosis, Neuronal degeneration, Oligodendrocyte, Pentoxifylline, Phosphodiesterase, Rolipram, Suzumura, Tnfa, Tnfa production, Transgenic mice, Tumor necrosis, Tumor necrosis factor.
Abstract
Abstract: Tumor necrosis factor α (TNFα) is considered to play a critical role in the development of various pathological processes in the central nervous system (CNS), such as neuronal degeneration, demyelination and HIV-related pathology. In order to search for the agents which suppress TNFα production in the CNS for future treatment of these pathological conditions, we examined the effects of ibudilast on TNFα production by murine microglia and astrocytes. Some actions of ibudilast are reportedly mediated by inhibition of type IV phosphodiesterase (PDE). Type IV PDE inhibitor has been shown to be the most effective for experimental autoimmune inflammatory demyelination. Therefore, we also determined the subtype of PDE inhibited by ibudilast. Ibudilast significantly and selectively suppressed TNFα production by microglia in a dose-dependent manner, without affecting their viability. The inhibition assay indicated that ibudilast is a rather selective inhibitor for type III PDE purified from brain, heart and kidney with moderate inhibitory activity against types I, II and IV PDEs from various tissues. Although it required 10 μM or higher concentrations to effectively suppress TNFα production in vitro, the combination of ibudilast with other subtypes of PDE inhibitors synergistically suppressed TNFα and nitric oxide production by microglia at 1 μM, a similar concentration that could be obtained in vivo at usual therapeutic dose. Thus, ibudilast, when used in a combination with other PDE inhibitors, will be useful for future strategies to treat intractable neurological diseases in which TNFα may play a causative role.
Url:
DOI: 10.1016/S0006-8993(99)01666-2
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream Istex, to step Corpus: 000353
- to stream Istex, to step Curation: 000320
- to stream Istex, to step Checkpoint: 000373
- to stream Main, to step Merge: 001958
- to stream Main, to step Curation: 001945
Le document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Ibudilast suppresses TNFα production by glial cells functioning mainly as type III phosphodiesterase inhibitor in the CNS</title><author><name sortKey="Suzumura, Akio" sort="Suzumura, Akio" uniqKey="Suzumura A" first="Akio" last="Suzumura">Akio Suzumura</name></author><author><name sortKey="Ito, Atsushi" sort="Ito, Atsushi" uniqKey="Ito A" first="Atsushi" last="Ito">Atsushi Ito</name></author><author><name sortKey="Yoshikawa, Minka" sort="Yoshikawa, Minka" uniqKey="Yoshikawa M" first="Minka" last="Yoshikawa">Minka Yoshikawa</name></author><author><name sortKey="Sawada, Makoto" sort="Sawada, Makoto" uniqKey="Sawada M" first="Makoto" last="Sawada">Makoto Sawada</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:A4BA999CFA2DF24D1F45D832D746635133586D1A</idno><date when="1999" year="1999">1999</date><idno type="doi">10.1016/S0006-8993(99)01666-2</idno><idno type="url">https://api.istex.fr/ark:/67375/6H6-NJLGW2F0-P/fulltext.pdf</idno><idno type="wicri:Area/Istex/Corpus">000353</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">000353</idno><idno type="wicri:Area/Istex/Curation">000320</idno><idno type="wicri:Area/Istex/Checkpoint">000373</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Checkpoint">000373</idno><idno type="wicri:doubleKey">0006-8993:1999:Suzumura A:ibudilast:suppresses:tnf</idno><idno type="wicri:Area/Main/Merge">001958</idno><idno type="wicri:Area/Main/Curation">001945</idno><idno type="wicri:Area/Main/Exploration">001945</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Ibudilast suppresses TNFα production by glial cells functioning mainly as type III phosphodiesterase inhibitor in the CNS</title><author><name sortKey="Suzumura, Akio" sort="Suzumura, Akio" uniqKey="Suzumura A" first="Akio" last="Suzumura">Akio Suzumura</name><affiliation wicri:level="1"><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Neurology, Nara Medical University, Shijo-cho, Kashihara, Nara 634-0813</wicri:regionArea><wicri:noRegion>Nara 634-0813</wicri:noRegion></affiliation></author><author><name sortKey="Ito, Atsushi" sort="Ito, Atsushi" uniqKey="Ito A" first="Atsushi" last="Ito">Atsushi Ito</name><affiliation wicri:level="1"><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Neurology, Nara Medical University, Shijo-cho, Kashihara, Nara 634-0813</wicri:regionArea><wicri:noRegion>Nara 634-0813</wicri:noRegion></affiliation></author><author><name sortKey="Yoshikawa, Minka" sort="Yoshikawa, Minka" uniqKey="Yoshikawa M" first="Minka" last="Yoshikawa">Minka Yoshikawa</name><affiliation wicri:level="1"><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Neurology, Nara Medical University, Shijo-cho, Kashihara, Nara 634-0813</wicri:regionArea><wicri:noRegion>Nara 634-0813</wicri:noRegion></affiliation></author><author><name sortKey="Sawada, Makoto" sort="Sawada, Makoto" uniqKey="Sawada M" first="Makoto" last="Sawada">Makoto Sawada</name><affiliation wicri:level="1"><country xml:lang="fr">Japon</country><wicri:regionArea>Joint Research Division for Therapies against Intractable Disease, Institute for Comprehensive Medical Sciences, Fujita Health University, Toyoake, Aichi 470-1192</wicri:regionArea><wicri:noRegion>Aichi 470-1192</wicri:noRegion></affiliation></author></analytic><monogr></monogr><series><title level="j">Brain Research</title><title level="j" type="abbrev">BRES</title><idno type="ISSN">0006-8993</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1999">1999</date><biblScope unit="volume">837</biblScope><biblScope unit="issue">1–2</biblScope><biblScope unit="page" from="203">203</biblScope><biblScope unit="page" to="212">212</biblScope></imprint><idno type="ISSN">0006-8993</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0006-8993</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Astrocyte</term><term>Cytokine</term><term>Microglia</term><term>Multiple sclerosis</term><term>Phosphodiesterase inhibitor</term><term>TNF</term></keywords><keywords scheme="Teeft" xml:lang="en"><term>Antigen expression</term><term>Antisense</term><term>Assay</term><term>Astrocyte</term><term>Brain research</term><term>Cell death</term><term>Cyclic</term><term>Cytokine</term><term>Cytokine production</term><term>Demyelination</term><term>Dipyridamole</term><term>Glial</term><term>Glial cells</term><term>Higher concentrations</term><term>Ibudilast</term><term>Immunol</term><term>Inflammatory demyelination</term><term>Inhibitor</term><term>Inhibitory activity</term><term>Inhibitory effects</term><term>Microglia</term><term>Mrna</term><term>Multiple sclerosis</term><term>Neuronal degeneration</term><term>Oligodendrocyte</term><term>Pentoxifylline</term><term>Phosphodiesterase</term><term>Rolipram</term><term>Suzumura</term><term>Tnfa</term><term>Tnfa production</term><term>Transgenic mice</term><term>Tumor necrosis</term><term>Tumor necrosis factor</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Abstract: Tumor necrosis factor α (TNFα) is considered to play a critical role in the development of various pathological processes in the central nervous system (CNS), such as neuronal degeneration, demyelination and HIV-related pathology. In order to search for the agents which suppress TNFα production in the CNS for future treatment of these pathological conditions, we examined the effects of ibudilast on TNFα production by murine microglia and astrocytes. Some actions of ibudilast are reportedly mediated by inhibition of type IV phosphodiesterase (PDE). Type IV PDE inhibitor has been shown to be the most effective for experimental autoimmune inflammatory demyelination. Therefore, we also determined the subtype of PDE inhibited by ibudilast. Ibudilast significantly and selectively suppressed TNFα production by microglia in a dose-dependent manner, without affecting their viability. The inhibition assay indicated that ibudilast is a rather selective inhibitor for type III PDE purified from brain, heart and kidney with moderate inhibitory activity against types I, II and IV PDEs from various tissues. Although it required 10 μM or higher concentrations to effectively suppress TNFα production in vitro, the combination of ibudilast with other subtypes of PDE inhibitors synergistically suppressed TNFα and nitric oxide production by microglia at 1 μM, a similar concentration that could be obtained in vivo at usual therapeutic dose. Thus, ibudilast, when used in a combination with other PDE inhibitors, will be useful for future strategies to treat intractable neurological diseases in which TNFα may play a causative role.</div></front></TEI><affiliations><list><country><li>Japon</li></country></list><tree><country name="Japon"><noRegion><name sortKey="Suzumura, Akio" sort="Suzumura, Akio" uniqKey="Suzumura A" first="Akio" last="Suzumura">Akio Suzumura</name></noRegion><name sortKey="Ito, Atsushi" sort="Ito, Atsushi" uniqKey="Ito A" first="Atsushi" last="Ito">Atsushi Ito</name><name sortKey="Sawada, Makoto" sort="Sawada, Makoto" uniqKey="Sawada M" first="Makoto" last="Sawada">Makoto Sawada</name><name sortKey="Yoshikawa, Minka" sort="Yoshikawa, Minka" uniqKey="Yoshikawa M" first="Minka" last="Yoshikawa">Minka Yoshikawa</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/CovidV2/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001945 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 001945 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Sante
|area= CovidV2
|flux= Main
|étape= Exploration
|type= RBID
|clé= ISTEX:A4BA999CFA2DF24D1F45D832D746635133586D1A
|texte= Ibudilast suppresses TNFα production by glial cells functioning mainly as type III phosphodiesterase inhibitor in the CNS
}}
| This area was generated with Dilib version V0.6.33. |  |