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Verfasst von:Chalaris, Athena [VerfasserIn]   i
 Adam, Nina [VerfasserIn]   i
 Sina, Christian [VerfasserIn]   i
 Rosenstiel, Philip [VerfasserIn]   i
 Lehmann-Koch, Judith [VerfasserIn]   i
 Schirmacher, Peter [VerfasserIn]   i
 Hartmann, Dieter [VerfasserIn]   i
 Cichy, Joanna [VerfasserIn]   i
 Gavrilova, Olga [VerfasserIn]   i
 Schreiber, Stefan [VerfasserIn]   i
 Jostock, Thomas [VerfasserIn]   i
 Matthews, Vance [VerfasserIn]   i
 Häsler, Robert [VerfasserIn]   i
 Becker, Christoph [VerfasserIn]   i
 Neurath, Markus F. [VerfasserIn]   i
 Reiss, Karina [VerfasserIn]   i
 Saftig, Paul [VerfasserIn]   i
 Scheller, Jürgen [VerfasserIn]   i
 Rose-John, Stefan [VerfasserIn]   i
Titel:Critical role of the disintegrin metalloprotease ADAM17 for intestinal inflammation and regeneration in mice
Verf.angabe:Athena Chalaris, Nina Adam, Christian Sina, Philip Rosenstiel, Judith Lehmann-Koch, Peter Schirmacher, Dieter Hartmann, Joanna Cichy, Olga Gavrilova, Stefan Schreiber, Thomas Jostock, Vance Matthews, Robert Häsler, Christoph Becker, Markus F. Neurath, Karina Reiss, Paul Saftig, Jürgen Scheller, and Stefan Rose-John
E-Jahr:2010
Jahr:5 July 2010
Umfang:8 S.
Fussnoten:Gesehen am 31.01.2023
Titel Quelle:Enthalten in: Journal of experimental medicine
Ort Quelle:New York, NY : Rockefeller Univ. Press, 1896
Jahr Quelle:2010
Band/Heft Quelle:207(2010), 8, Seite 1617-1624
ISSN Quelle:1540-9538
Abstract:The protease a disintegrin and metalloprotease (ADAM) 17 cleaves tumor necrosis factor (TNF), L-selectin, and epidermal growth factor receptor (EGF-R) ligands from the plasma membrane. ADAM17 is expressed in most tissues and is up-regulated during inflammation and cancer. ADAM17-deficient mice are not viable. Conditional ADAM17 knockout models demonstrated proinflammatory activities of ADAM17 in septic shock via shedding of TNF. We used a novel gene targeting strategy to generate mice with dramatically reduced ADAM17 levels in all tissues. The resulting mice called ADAM17(ex/ex) were viable, showed compromised shedding of ADAM17 substrates from the cell surface, and developed eye, heart, and skin defects as a consequence of impaired EGF-R signaling caused by failure of shedding of EGF-R ligands. Unexpectedly, although the intestine of unchallenged homozygous ADAM17(ex/ex) mice was normal, ADAM17(ex/ex) mice showed substantially increased susceptibility to inflammation in dextran sulfate sodium colitis. This was a result of impaired shedding of EGF-R ligands resulting in failure to phosphorylate STAT3 via the EGF-R and, consequently, in defective regeneration of epithelial cells and breakdown of the intestinal barrier. Besides regulating the systemic availability of the proinflammatory cytokine TNF, our results demonstrate that ADAM17 is needed for vital regenerative activities during the immune response. Thus, our mouse model will help investigate ADAM17 as a potential drug target.
DOI:doi:10.1084/jem.20092366
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext: https://doi.org/10.1084/jem.20092366
 DOI: https://doi.org/10.1084/jem.20092366
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:ADAM Proteins
 ADAM17 Protein
 Animal Structures
 Animals
 Brain
 Cell Proliferation
 Chemokines
 Colon
 Cyclin D1
 Cytokines
 Dextran Sulfate
 Epithelial Cells
 Female
 Gene Expression
 Gene Expression Profiling
 Inflammatory Bowel Diseases
 Intestinal Mucosa
 L-Selectin
 Liver
 Mammary Glands, Animal
 Mice
 Mice, Inbred C57BL
 Mice, Transgenic
 Permeability
 Peroxidase
 Phosphorylation
 Receptors, Tumor Necrosis Factor, Type II
 Regeneration
 STAT3 Transcription Factor
 Transforming Growth Factor alpha
 Tumor Necrosis Factor-alpha
K10plus-PPN:1832812111
Verknüpfungen:→ Zeitschrift

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