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doi:10.22028/D291-32084
Titel: | The iRhom2/ADAM17 Axis Attenuates Bacterial Uptake by Phagocytes in a Cell Autonomous Manner |
VerfasserIn: | Seifert, Anke Wozniak, Justyna Düsterhöft, Stefan Kasparek, Petr Sedlacek, Radislav Dreschers, Stephan Orlikowsky, Thorsten W. Yildiz, Daniela Ludwig, Andreas |
Sprache: | Englisch |
Titel: | International Journal of Molecular Sciences |
Bandnummer: | 21 |
Heft: | 17 |
Verlag/Plattform: | MDPI |
Erscheinungsjahr: | 2020 |
Freie Schlagwörter: | metalloproteinase ADAM17 iRhom2 bacterial phagocytosis inflammation infection shedding chemokines phagocytes |
DDC-Sachgruppe: | 610 Medizin, Gesundheit |
Dokumenttyp: | Journalartikel / Zeitschriftenartikel |
Abstract: | Uptake of bacteria by phagocytes is a crucial step in innate immune defence. Members of the disintegrin and metalloproteinase (ADAM) family critically control the immune response by limited proteolysis of surface expressed mediator molecules. Here, we investigated the significance of ADAM17 and its regulatory adapter molecule iRhom2 for bacterial uptake by phagocytes. Inhibition of metalloproteinase activity led to increased phagocytosis of pHrodo labelled Gram-negative and -positive bacteria (E. coli and S. aureus, respectively) by human and murine monocytic cell lines or primary phagocytes. Bone marrow-derived macrophages showed enhanced uptake of heat-inactivated and living E. coli when they lacked either ADAM17 or iRhom2 but not upon ADAM10-deficiency. In monocytic THP-1 cells, corresponding short hairpin RNA (shRNA)-mediated knockdown confirmed that ADAM17, but not ADAM10, promoted phagocytosis of E. coli. The augmented bacterial uptake occurred in a cell autonomous manner and was accompanied by increased release of the chemokine CXCL8, less TNFα release and only minimal changes in the surface expression of the receptors TNFR1, TLR6 and CD36. Inhibition experiments indicated that the enhanced bacterial phagocytosis after ADAM17 knockdown was partially dependent on TNFα-activity but not on CXCL8. This novel role of ADAM17 in bacterial uptake needs to be considered in the development of ADAM17 inhibitors as therapeutics. |
DOI der Erstveröffentlichung: | 10.3390/ijms21175978 |
Link zu diesem Datensatz: | urn:nbn:de:bsz:291--ds-320841 hdl:20.500.11880/30423 http://dx.doi.org/10.22028/D291-32084 |
ISSN: | 1422-0067 |
Datum des Eintrags: | 25-Jan-2021 |
Bezeichnung des in Beziehung stehenden Objekts: | Supplementary Materials |
In Beziehung stehendes Objekt: | http://www.mdpi.com/1422-0067/21/17/5978/s1 |
Fakultät: | M - Medizinische Fakultät ZE - Zentrale Einrichtungen |
Fachrichtung: | M - Experimentelle und Klinische Pharmakologie und Toxikologie ZE - Zentrum für Human- und Molekularbiologie (ZHMB) |
Professur: | M - Jun.-Prof. Dr. Daniela Yildiz ZE - Sonstige |
Sammlung: | SciDok - Der Wissenschaftsserver der Universität des Saarlandes |
Dateien zu diesem Datensatz:
Datei | Beschreibung | Größe | Format | |
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ijms-21-05978-v2.pdf | 2,69 MB | Adobe PDF | Öffnen/Anzeigen |
Diese Ressource wurde unter folgender Copyright-Bestimmung veröffentlicht: Lizenz von Creative Commons