Oligonucleotides antisense to the interleukin 1 receptor mRNA block the effects of interleukin 1 in cultured murine and human fibroblasts and in mice.
Identifieur interne : 000589 ( Ncbi/Checkpoint ); précédent : 000588; suivant : 000590Oligonucleotides antisense to the interleukin 1 receptor mRNA block the effects of interleukin 1 in cultured murine and human fibroblasts and in mice.
Auteurs : R M Burch [États-Unis] ; L C MahanSource :
- The Journal of clinical investigation [ 0021-9738 ] ; 1991.
Descripteurs français
- KwdFr :
- ARN messager (génétique), Animaux, Cellules cultivées, Dinoprostone (biosynthèse), Données de séquences moléculaires, Fibroblastes (), Humains, Interleukine-1 (antagonistes et inhibiteurs), Interleukine-1 (métabolisme), Liposomes (administration et posologie), Oligonucléotides antisens (pharmacologie), Relation dose-effet des médicaments, Récepteurs immunologiques (analyse), Récepteurs immunologiques (génétique), Récepteurs immunologiques (physiologie), Récepteurs à l'interleukine-1, Souris, Séquence nucléotidique.
- MESH :
- administration et posologie : Liposomes.
- analyse : Récepteurs immunologiques.
- antagonistes et inhibiteurs : Interleukine-1.
- biosynthèse : Dinoprostone.
- génétique : ARN messager, Récepteurs immunologiques.
- métabolisme : Interleukine-1.
- pharmacologie : Oligonucléotides antisens.
- physiologie : Récepteurs immunologiques.
- Animaux, Cellules cultivées, Données de séquences moléculaires, Fibroblastes, Humains, Relation dose-effet des médicaments, Récepteurs à l'interleukine-1, Souris, Séquence nucléotidique.
English descriptors
- KwdEn :
- Animals, Base Sequence, Cells, Cultured, Dinoprostone (biosynthesis), Dose-Response Relationship, Drug, Fibroblasts (drug effects), Humans, Interleukin-1 (antagonists & inhibitors), Interleukin-1 (metabolism), Liposomes (administration & dosage), Mice, Molecular Sequence Data, Oligonucleotides, Antisense (pharmacology), RNA, Messenger (genetics), Receptors, Immunologic (analysis), Receptors, Immunologic (genetics), Receptors, Immunologic (physiology), Receptors, Interleukin-1.
- MESH :
- chemical , administration & dosage : Liposomes.
- chemical , analysis : Receptors, Immunologic.
- chemical , antagonists & inhibitors : Interleukin-1.
- chemical , biosynthesis : Dinoprostone.
- drug effects : Fibroblasts.
- chemical , genetics : RNA, Messenger, Receptors, Immunologic.
- chemical , metabolism : Interleukin-1.
- chemical , pharmacology : Oligonucleotides, Antisense.
- chemical , physiology : Receptors, Immunologic.
- Animals, Base Sequence, Cells, Cultured, Dose-Response Relationship, Drug, Humans, Mice, Molecular Sequence Data, Receptors, Interleukin-1.
Abstract
Phosphodiester and phosphorothioate oligodeoxynucleotides (18 mers) were constructed antisense to sequences of the recently cloned murine and human IL-1 receptors. Murine antisense oligonucleotides inhibited IL-1-stimulated PGE2 synthesis by murine fibroblasts in culture in a time (days) and concentration-dependent (3 microM-30 microM) fashion. Murine sense oligonucleotide and an oligonucleotide antisense to human IL-1 receptor were without effect. Moreover, murine antisense oligonucleotides did not affect tumor necrosis factor- or bradykinin-stimulated PGE2 synthesis by murine fibroblasts. Similarly, antisense oligonucleotides to the human, but not the murine, IL-1 receptor inhibited IL-1-stimulated PGE2 synthesis by cultured human fibroblasts. The attenuation of the cellular response to IL-1 caused by the antisense oligonucleotides correlated with a loss in cell surface receptors for IL-1, without any change in the number of bradykinin receptors on these cells. When antisense oligonucleotides were encapsulated in liposomes, they blocked completely the appearance of newly synthesized IL-1 receptors and IL-1-stimulated PGE2 synthesis. In mice, subcutaneous injection with an oligonucleotide antisense to the murine IL-1 receptor markedly inhibited the infiltration of neutrophils in response to subsequent injection of IL-1. These data suggest that antisense oligodeoxynucleotides may share a role in the design of antiinflammatory therapeutics.
DOI: 10.1172/JCI115421
PubMed: 1833422
Affiliations:
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pubmed:1833422Le document en format XML
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Corporation, Baltimore, Maryland 21224.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Nova Pharmaceutical Corporation, Baltimore</wicri:cityArea></affiliation></author><author><name sortKey="Mahan, L C" sort="Mahan, L C" uniqKey="Mahan L" first="L C" last="Mahan">L C Mahan</name></author></analytic><series><title level="j">The Journal of clinical investigation</title><idno type="ISSN">0021-9738</idno><imprint><date when="1991" type="published">1991</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Base Sequence</term><term>Cells, Cultured</term><term>Dinoprostone (biosynthesis)</term><term>Dose-Response Relationship, Drug</term><term>Fibroblasts (drug effects)</term><term>Humans</term><term>Interleukin-1 (antagonists & inhibitors)</term><term>Interleukin-1 (metabolism)</term><term>Liposomes (administration & dosage)</term><term>Mice</term><term>Molecular Sequence Data</term><term>Oligonucleotides, Antisense (pharmacology)</term><term>RNA, Messenger (genetics)</term><term>Receptors, Immunologic (analysis)</term><term>Receptors, Immunologic (genetics)</term><term>Receptors, Immunologic (physiology)</term><term>Receptors, Interleukin-1</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>ARN messager (génétique)</term><term>Animaux</term><term>Cellules cultivées</term><term>Dinoprostone (biosynthèse)</term><term>Données de séquences moléculaires</term><term>Fibroblastes ()</term><term>Humains</term><term>Interleukine-1 (antagonistes et inhibiteurs)</term><term>Interleukine-1 (métabolisme)</term><term>Liposomes (administration et posologie)</term><term>Oligonucléotides antisens (pharmacologie)</term><term>Relation dose-effet des médicaments</term><term>Récepteurs immunologiques (analyse)</term><term>Récepteurs immunologiques (génétique)</term><term>Récepteurs immunologiques (physiologie)</term><term>Récepteurs à l'interleukine-1</term><term>Souris</term><term>Séquence nucléotidique</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Liposomes</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analysis" xml:lang="en"><term>Receptors, Immunologic</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Interleukin-1</term></keywords><keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Dinoprostone</term></keywords><keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Liposomes</term></keywords><keywords scheme="MESH" qualifier="analyse" xml:lang="fr"><term>Récepteurs immunologiques</term></keywords><keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Interleukine-1</term></keywords><keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr"><term>Dinoprostone</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Fibroblasts</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>RNA, Messenger</term><term>Receptors, Immunologic</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>ARN messager</term><term>Récepteurs immunologiques</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Interleukin-1</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Interleukine-1</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Oligonucléotides antisens</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Oligonucleotides, Antisense</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Récepteurs immunologiques</term></keywords><keywords scheme="MESH" type="chemical" qualifier="physiology" xml:lang="en"><term>Receptors, Immunologic</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Base Sequence</term><term>Cells, Cultured</term><term>Dose-Response Relationship, Drug</term><term>Humans</term><term>Mice</term><term>Molecular Sequence Data</term><term>Receptors, Interleukin-1</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Cellules cultivées</term><term>Données de séquences moléculaires</term><term>Fibroblastes</term><term>Humains</term><term>Relation dose-effet des médicaments</term><term>Récepteurs à l'interleukine-1</term><term>Souris</term><term>Séquence nucléotidique</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Phosphodiester and phosphorothioate oligodeoxynucleotides (18 mers) were constructed antisense to sequences of the recently cloned murine and human IL-1 receptors. Murine antisense oligonucleotides inhibited IL-1-stimulated PGE2 synthesis by murine fibroblasts in culture in a time (days) and concentration-dependent (3 microM-30 microM) fashion. Murine sense oligonucleotide and an oligonucleotide antisense to human IL-1 receptor were without effect. Moreover, murine antisense oligonucleotides did not affect tumor necrosis factor- or bradykinin-stimulated PGE2 synthesis by murine fibroblasts. Similarly, antisense oligonucleotides to the human, but not the murine, IL-1 receptor inhibited IL-1-stimulated PGE2 synthesis by cultured human fibroblasts. The attenuation of the cellular response to IL-1 caused by the antisense oligonucleotides correlated with a loss in cell surface receptors for IL-1, without any change in the number of bradykinin receptors on these cells. When antisense oligonucleotides were encapsulated in liposomes, they blocked completely the appearance of newly synthesized IL-1 receptors and IL-1-stimulated PGE2 synthesis. In mice, subcutaneous injection with an oligonucleotide antisense to the murine IL-1 receptor markedly inhibited the infiltration of neutrophils in response to subsequent injection of IL-1. These data suggest that antisense oligodeoxynucleotides may share a role in the design of antiinflammatory therapeutics.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Maryland</li></region></list><tree><noCountry><name sortKey="Mahan, L C" sort="Mahan, L C" uniqKey="Mahan L" first="L C" last="Mahan">L C Mahan</name></noCountry><country name="États-Unis"><region name="Maryland"><name sortKey="Burch, R M" sort="Burch, R M" uniqKey="Burch R" first="R M" last="Burch">R M Burch</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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