An interleukin 12 p40-IgG2b fusion protein abrogates T cell mediated inflammation: anti-inflammatory activity in Crohn’s disease and experimental colitis in vivo
Identifieur interne : 000B22 ( Main/Exploration ); précédent : 000B21; suivant : 000B23An interleukin 12 p40-IgG2b fusion protein abrogates T cell mediated inflammation: anti-inflammatory activity in Crohn’s disease and experimental colitis in vivo
Auteurs : A. Stallmach [Allemagne] ; T. Marth [Allemagne] ; B. Wei [Allemagne] ; B M Wittig [Allemagne] ; A. Hombach [Allemagne] ; C. Schmidt [Allemagne] ; M. Neurath [Allemagne] ; M. Zeitz [Allemagne] ; S. Zeuzem [Allemagne] ; H. Abken [Allemagne]Source :
- Gut [ 0017-5749 ] ; 2004-03.
English descriptors
- KwdEn :
- 5-ASA, 5-aminosalicylic acid, CD, Crohn’s disease, Crohn’s disease, IFN-γ, interferon γ, IL, interleukin, LPMNC, lamina propria mononuclear cells, PBL, peripheral blood lymphocytes, PBMNC, peripheral blood mononuclear cells, PBS, phosphate buffered saline, PCR, polymerase chain reaction, PMA, phorbol myristate acetate, TNBS, 2,4,6,-trinitrobenzene sulphonic acid, TNF-α, tumour necrosis factor α, fusion protein, inflammatory bowel disease, interleukin 12, mAb, monoclonal antibody.
- Teeft :
- Active disease, Apoptosis, Apoptotic, Apoptotic cells, Bowel, Cdna, Cell proliferation, Colitis, Colitis mice, Colon specimens, Colonic, Conglomerate, Cytokine, Deficient mice, Experimental models, Facs analysis, Flow cytometry, Fusion, Fusion protein, Gastroenterology, Glucocorticoid, High concentrations, Igg2b, Ileocaecal, Ileocaecal conglomerate tumour, Ileocaecal part resection, Immune response, Immunol, Independent experiments, Inflammation, Inflammatory, Inflammatory bowel disease, Interleukin, Internal medicine, Intestinal, Intestinal inflammation, Intracellular cytokines, Lamina, Lamina propria, Lpmnc, Lymphocyte, Mouse, Mucosal, Peripheral blood lymphocytes, Phorbol myristate acetate, Positive cells, Primer, Propria, Receptor, Receptor binding site, Recombinant, Resection, Stallmach, Stricture, Stricture resection, Subunit, Sulphonic acid, Terminal ileum, Tnbs, Tnbs colitic mice, Tnbs colitis, Tnbs colitis mice, Tumour, Tumour necrosis factor.
Abstract
Background and aims: Interleukin-12 (IL-12), a p35/p40 heterodimer, plays a pivotal role in the immune response in Crohn’s disease (CD). Since IL-12 p40 dimers act as IL-12 antagonists, we assayed p40 dimer proteins to modulate chronic intestinal inflammation. Methods: We generated a fusion protein consisting of the IL-12(p40) subunit fused to the constant region of IgG2b. IL-12(p40)-IgG2b was tested in a murine 2,4,6,-trinitrobenzene sulphonic acid (TNBS) colitis model and in lamina propria mononuclear cells (LPMNC) from patients with CD in vitro. Results: Dimeric IL-12(p40)-IgG2b fusion protein bound specifically to the IL-12 receptor. In concentrations <10−7 M, it acted as an IL-12 antagonist as it inhibited interferon γ (IFN-γ) secretion, suppressed proliferation, and increased apoptosis of LPMNC from patients with CD. However, in concentrations >10−6 M, IL-12(p40)-IgG2b increased IFN-γ secretion and lymphocyte proliferation thereby acting as an IL-12 agonist. In TNBS colitic mice, IL-12(p40)-IgG2b decreased mortality (10% v 68%), prevented body weight loss, reduced tumour necrosis factor α, and increased IL-10 secretion. Conclusions: The IL-12(p40)-IgG2b fusion protein has dichotomic properties as a specific IL-12 antagonist and selective repressor of mucosal inflammation at low concentration and as an IL-12 agonist at high concentration.
Url:
DOI: 10.1136/gut.2003.020107
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream Istex, to step Corpus: 000B09
- to stream Istex, to step Curation: 000A53
- to stream Istex, to step Checkpoint: 000917
- to stream Main, to step Merge: 000B22
- to stream Main, to step Curation: 000B22
Le document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">An interleukin 12 p40-IgG2b fusion protein abrogates T cell mediated inflammation: anti-inflammatory activity in Crohn’s disease and experimental colitis in vivo</title>
<author><name sortKey="Stallmach, A" sort="Stallmach, A" uniqKey="Stallmach A" first="A" last="Stallmach">A. Stallmach</name>
</author>
<author><name sortKey="Marth, T" sort="Marth, T" uniqKey="Marth T" first="T" last="Marth">T. Marth</name>
</author>
<author><name sortKey="Wei, B" sort="Wei, B" uniqKey="Wei B" first="B" last="Wei">B. Wei</name>
</author>
<author><name sortKey="Wittig, B M" sort="Wittig, B M" uniqKey="Wittig B" first="B M" last="Wittig">B M Wittig</name>
</author>
<author><name sortKey="Hombach, A" sort="Hombach, A" uniqKey="Hombach A" first="A" last="Hombach">A. Hombach</name>
</author>
<author><name sortKey="Schmidt, C" sort="Schmidt, C" uniqKey="Schmidt C" first="C" last="Schmidt">C. Schmidt</name>
</author>
<author><name sortKey="Neurath, M" sort="Neurath, M" uniqKey="Neurath M" first="M" last="Neurath">M. Neurath</name>
</author>
<author><name sortKey="Zeitz, M" sort="Zeitz, M" uniqKey="Zeitz M" first="M" last="Zeitz">M. Zeitz</name>
</author>
<author><name sortKey="Zeuzem, S" sort="Zeuzem, S" uniqKey="Zeuzem S" first="S" last="Zeuzem">S. Zeuzem</name>
</author>
<author><name sortKey="Abken, H" sort="Abken, H" uniqKey="Abken H" first="H" last="Abken">H. Abken</name>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">ISTEX</idno>
<idno type="RBID">ISTEX:68EA40E2B9E8CE5BC0812327B7D680310BDAEAAA</idno>
<date when="2004" year="2004">2004</date>
<idno type="doi">10.1136/gut.2003.020107</idno>
<idno type="url">https://api.istex.fr/document/68EA40E2B9E8CE5BC0812327B7D680310BDAEAAA/fulltext/pdf</idno>
<idno type="wicri:Area/Istex/Corpus">000B09</idno>
<idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">000B09</idno>
<idno type="wicri:Area/Istex/Curation">000A53</idno>
<idno type="wicri:Area/Istex/Checkpoint">000917</idno>
<idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Checkpoint">000917</idno>
<idno type="wicri:doubleKey">0017-5749:2004:Stallmach A:an:interleukin:p</idno>
<idno type="wicri:Area/Main/Merge">000B22</idno>
<idno type="wicri:Area/Main/Curation">000B22</idno>
<idno type="wicri:Area/Main/Exploration">000B22</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">An interleukin 12 p40-IgG2b fusion protein abrogates T cell mediated inflammation: anti-inflammatory activity in Crohn’s disease and experimental colitis in vivo</title>
<author><name sortKey="Stallmach, A" sort="Stallmach, A" uniqKey="Stallmach A" first="A" last="Stallmach">A. Stallmach</name>
<affiliation wicri:level="1"><country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Internal Medicine II, Saarland University, Homburg</wicri:regionArea>
<wicri:noRegion>Homburg</wicri:noRegion>
<wicri:noRegion>Homburg</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Marth, T" sort="Marth, T" uniqKey="Marth T" first="T" last="Marth">T. Marth</name>
<affiliation wicri:level="1"><country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Internal Medicine II, Saarland University, Homburg</wicri:regionArea>
<wicri:noRegion>Homburg</wicri:noRegion>
<wicri:noRegion>Homburg</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Wei, B" sort="Wei, B" uniqKey="Wei B" first="B" last="Wei">B. Wei</name>
<affiliation wicri:level="1"><country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Internal Medicine II, Saarland University, Homburg</wicri:regionArea>
<wicri:noRegion>Homburg</wicri:noRegion>
<wicri:noRegion>Homburg</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Wittig, B M" sort="Wittig, B M" uniqKey="Wittig B" first="B M" last="Wittig">B M Wittig</name>
<affiliation wicri:level="3"><country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Internal Medicine I, Free University Berlin, Berlin</wicri:regionArea>
<placeName><region type="land" nuts="3">Berlin</region>
<settlement type="city">Berlin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Hombach, A" sort="Hombach, A" uniqKey="Hombach A" first="A" last="Hombach">A. Hombach</name>
<affiliation wicri:level="1"><country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Tumour Genetics, Clinic I for Internal Medicine, University of Cologne</wicri:regionArea>
<wicri:noRegion>University of Cologne</wicri:noRegion>
<wicri:noRegion>University of Cologne</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Schmidt, C" sort="Schmidt, C" uniqKey="Schmidt C" first="C" last="Schmidt">C. Schmidt</name>
<affiliation wicri:level="1"><country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Internal Medicine II, Saarland University, Homburg</wicri:regionArea>
<wicri:noRegion>Homburg</wicri:noRegion>
<wicri:noRegion>Homburg</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Neurath, M" sort="Neurath, M" uniqKey="Neurath M" first="M" last="Neurath">M. Neurath</name>
<affiliation wicri:level="1"><country xml:lang="fr">Allemagne</country>
<wicri:regionArea>I Medical Clinic, University of Mainz</wicri:regionArea>
<wicri:noRegion>University of Mainz</wicri:noRegion>
<wicri:noRegion>University of Mainz</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Zeitz, M" sort="Zeitz, M" uniqKey="Zeitz M" first="M" last="Zeitz">M. Zeitz</name>
<affiliation wicri:level="3"><country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Internal Medicine I, Free University Berlin, Berlin</wicri:regionArea>
<placeName><region type="land" nuts="3">Berlin</region>
<settlement type="city">Berlin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Zeuzem, S" sort="Zeuzem, S" uniqKey="Zeuzem S" first="S" last="Zeuzem">S. Zeuzem</name>
<affiliation wicri:level="1"><country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Internal Medicine II, Saarland University, Homburg</wicri:regionArea>
<wicri:noRegion>Homburg</wicri:noRegion>
<wicri:noRegion>Homburg</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Abken, H" sort="Abken, H" uniqKey="Abken H" first="H" last="Abken">H. Abken</name>
<affiliation wicri:level="1"><country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Tumour Genetics, Clinic I for Internal Medicine, University of Cologne</wicri:regionArea>
<wicri:noRegion>University of Cologne</wicri:noRegion>
<wicri:noRegion>University of Cologne</wicri:noRegion>
</affiliation>
</author>
</analytic>
<monogr></monogr>
<series><title level="j">Gut</title>
<title level="j" type="abbrev">Gut</title>
<idno type="ISSN">0017-5749</idno>
<idno type="eISSN">1468-3288</idno>
<imprint><publisher>BMJ Publishing Group Ltd and British Society of Gastroenterology</publisher>
<date type="published" when="2004-03">2004-03</date>
<biblScope unit="volume">53</biblScope>
<biblScope unit="issue">3</biblScope>
<biblScope unit="page" from="339">339</biblScope>
</imprint>
<idno type="ISSN">0017-5749</idno>
</series>
<idno type="istex">68EA40E2B9E8CE5BC0812327B7D680310BDAEAAA</idno>
<idno type="DOI">10.1136/gut.2003.020107</idno>
<idno type="href">gutjnl-53-339.pdf</idno>
<idno type="PMID">14960512</idno>
<idno type="local">0530339</idno>
</biblStruct>
</sourceDesc>
<seriesStmt><idno type="ISSN">0017-5749</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>5-ASA, 5-aminosalicylic acid</term>
<term>CD, Crohn’s disease</term>
<term>Crohn’s disease</term>
<term>IFN-γ, interferon γ</term>
<term>IL, interleukin</term>
<term>LPMNC, lamina propria mononuclear cells</term>
<term>PBL, peripheral blood lymphocytes</term>
<term>PBMNC, peripheral blood mononuclear cells</term>
<term>PBS, phosphate buffered saline</term>
<term>PCR, polymerase chain reaction</term>
<term>PMA, phorbol myristate acetate</term>
<term>TNBS, 2,4,6,-trinitrobenzene sulphonic acid</term>
<term>TNF-α, tumour necrosis factor α</term>
<term>fusion protein</term>
<term>inflammatory bowel disease</term>
<term>interleukin 12</term>
<term>mAb, monoclonal antibody</term>
</keywords>
<keywords scheme="Teeft" xml:lang="en"><term>Active disease</term>
<term>Apoptosis</term>
<term>Apoptotic</term>
<term>Apoptotic cells</term>
<term>Bowel</term>
<term>Cdna</term>
<term>Cell proliferation</term>
<term>Colitis</term>
<term>Colitis mice</term>
<term>Colon specimens</term>
<term>Colonic</term>
<term>Conglomerate</term>
<term>Cytokine</term>
<term>Deficient mice</term>
<term>Experimental models</term>
<term>Facs analysis</term>
<term>Flow cytometry</term>
<term>Fusion</term>
<term>Fusion protein</term>
<term>Gastroenterology</term>
<term>Glucocorticoid</term>
<term>High concentrations</term>
<term>Igg2b</term>
<term>Ileocaecal</term>
<term>Ileocaecal conglomerate tumour</term>
<term>Ileocaecal part resection</term>
<term>Immune response</term>
<term>Immunol</term>
<term>Independent experiments</term>
<term>Inflammation</term>
<term>Inflammatory</term>
<term>Inflammatory bowel disease</term>
<term>Interleukin</term>
<term>Internal medicine</term>
<term>Intestinal</term>
<term>Intestinal inflammation</term>
<term>Intracellular cytokines</term>
<term>Lamina</term>
<term>Lamina propria</term>
<term>Lpmnc</term>
<term>Lymphocyte</term>
<term>Mouse</term>
<term>Mucosal</term>
<term>Peripheral blood lymphocytes</term>
<term>Phorbol myristate acetate</term>
<term>Positive cells</term>
<term>Primer</term>
<term>Propria</term>
<term>Receptor</term>
<term>Receptor binding site</term>
<term>Recombinant</term>
<term>Resection</term>
<term>Stallmach</term>
<term>Stricture</term>
<term>Stricture resection</term>
<term>Subunit</term>
<term>Sulphonic acid</term>
<term>Terminal ileum</term>
<term>Tnbs</term>
<term>Tnbs colitic mice</term>
<term>Tnbs colitis</term>
<term>Tnbs colitis mice</term>
<term>Tumour</term>
<term>Tumour necrosis factor</term>
</keywords>
</textClass>
<langUsage><language ident="en">en</language>
</langUsage>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Background and aims: Interleukin-12 (IL-12), a p35/p40 heterodimer, plays a pivotal role in the immune response in Crohn’s disease (CD). Since IL-12 p40 dimers act as IL-12 antagonists, we assayed p40 dimer proteins to modulate chronic intestinal inflammation. Methods: We generated a fusion protein consisting of the IL-12(p40) subunit fused to the constant region of IgG2b. IL-12(p40)-IgG2b was tested in a murine 2,4,6,-trinitrobenzene sulphonic acid (TNBS) colitis model and in lamina propria mononuclear cells (LPMNC) from patients with CD in vitro. Results: Dimeric IL-12(p40)-IgG2b fusion protein bound specifically to the IL-12 receptor. In concentrations <10−7 M, it acted as an IL-12 antagonist as it inhibited interferon γ (IFN-γ) secretion, suppressed proliferation, and increased apoptosis of LPMNC from patients with CD. However, in concentrations >10−6 M, IL-12(p40)-IgG2b increased IFN-γ secretion and lymphocyte proliferation thereby acting as an IL-12 agonist. In TNBS colitic mice, IL-12(p40)-IgG2b decreased mortality (10% v 68%), prevented body weight loss, reduced tumour necrosis factor α, and increased IL-10 secretion. Conclusions: The IL-12(p40)-IgG2b fusion protein has dichotomic properties as a specific IL-12 antagonist and selective repressor of mucosal inflammation at low concentration and as an IL-12 agonist at high concentration.</div>
</front>
</TEI>
<affiliations><list><country><li>Allemagne</li>
</country>
<region><li>Berlin</li>
</region>
<settlement><li>Berlin</li>
</settlement>
</list>
<tree><country name="Allemagne"><noRegion><name sortKey="Stallmach, A" sort="Stallmach, A" uniqKey="Stallmach A" first="A" last="Stallmach">A. Stallmach</name>
</noRegion>
<name sortKey="Abken, H" sort="Abken, H" uniqKey="Abken H" first="H" last="Abken">H. Abken</name>
<name sortKey="Hombach, A" sort="Hombach, A" uniqKey="Hombach A" first="A" last="Hombach">A. Hombach</name>
<name sortKey="Marth, T" sort="Marth, T" uniqKey="Marth T" first="T" last="Marth">T. Marth</name>
<name sortKey="Neurath, M" sort="Neurath, M" uniqKey="Neurath M" first="M" last="Neurath">M. Neurath</name>
<name sortKey="Schmidt, C" sort="Schmidt, C" uniqKey="Schmidt C" first="C" last="Schmidt">C. Schmidt</name>
<name sortKey="Wei, B" sort="Wei, B" uniqKey="Wei B" first="B" last="Wei">B. Wei</name>
<name sortKey="Wittig, B M" sort="Wittig, B M" uniqKey="Wittig B" first="B M" last="Wittig">B M Wittig</name>
<name sortKey="Zeitz, M" sort="Zeitz, M" uniqKey="Zeitz M" first="M" last="Zeitz">M. Zeitz</name>
<name sortKey="Zeuzem, S" sort="Zeuzem, S" uniqKey="Zeuzem S" first="S" last="Zeuzem">S. Zeuzem</name>
</country>
</tree>
</affiliations>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sarre/explor/MusicSarreV3/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000B22 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000B22 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Wicri/Sarre |area= MusicSarreV3 |flux= Main |étape= Exploration |type= RBID |clé= ISTEX:68EA40E2B9E8CE5BC0812327B7D680310BDAEAAA |texte= An interleukin 12 p40-IgG2b fusion protein abrogates T cell mediated inflammation: anti-inflammatory activity in Crohn’s disease and experimental colitis in vivo }}
This area was generated with Dilib version V0.6.33. |