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doi:10.22028/D291-35586
Titel: | Chemokine CCL9 Is Upregulated Early in Chronic Kidney Disease and Counteracts Kidney Inflammation and Fibrosis |
VerfasserIn: | Hemmers, Christian Schulte, Corinna Wollenhaupt, Julia Wong, Dickson W. L. Harlacher, Eva Orth-Alampour, Setareh Klinkhammer, Barbara Mara Schirmer, Stephan H. Böhm, Michael Marx, Nikolaus Speer, Thimoteus Boor, Peter Jankowski, Joachim Noels, Heidi |
Sprache: | Englisch |
Titel: | Biomedicines |
Bandnummer: | 10 |
Heft: | 2 |
Verlag/Plattform: | MDPI |
Erscheinungsjahr: | 2022 |
Freie Schlagwörter: | chronic kidney disease chemokine inflammation macrophage CCL6 CCL9 MIP-1γ fibrosis collagen |
DDC-Sachgruppe: | 610 Medizin, Gesundheit |
Dokumenttyp: | Journalartikel / Zeitschriftenartikel |
Abstract: | Inflammation and fibrosis play an important pathophysiological role in chronic kidney disease (CKD), with pro-inflammatory mediators and leukocytes promoting organ damage with subsequent fibrosis. Since chemokines are the main regulators of leukocyte chemotaxis and tissue inflammation, we performed systemic chemokine profiling in early CKD in mice. This revealed (C-C motif) ligands 6 and 9 (CCL6 and CCL9) as the most upregulated chemokines, with significantly higher levels of both chemokines in blood (CCL6: 3–4 fold; CCL9: 3–5 fold) as well as kidney as confirmed by Enzyme-linked Immunosorbent Assay (ELISA) in two additional CKD models. Chemokine treatment in a mouse model of early adenine-induced CKD almost completely abolished the CKD-induced infiltration of macrophages and myeloid cells in the kidney without impact on circulating leukocyte numbers. The other way around, especially CCL9-blockade aggravated monocyte and macrophage accumulation in kidney during CKD development, without impact on the ratio of M1-to-M2 macrophages. In parallel, CCL9-blockade raised serum creatinine and urea levels as readouts of kidney dysfunction. It also exacerbated CKD-induced expression of collagen (3.2-fold) and the pro-inflammatory chemokines CCL2 (1.8-fold) and CCL3 (2.1-fold) in kidney. Altogether, this study reveals for the first time that chemokines CCL6 and CCL9 are upregulated early in experimental CKD, with CCL9-blockade during CKD initiation enhancing kidney inflammation and fibrosis. |
DOI der Erstveröffentlichung: | 10.3390/biomedicines10020420 |
Link zu diesem Datensatz: | urn:nbn:de:bsz:291--ds-355864 hdl:20.500.11880/32497 http://dx.doi.org/10.22028/D291-35586 |
ISSN: | 2227-9059 |
Datum des Eintrags: | 1-Mär-2022 |
Bezeichnung des in Beziehung stehenden Objekts: | Supplementary Materials |
In Beziehung stehendes Objekt: | https://www.mdpi.com/article/10.3390/biomedicines10020420/s1 |
Fakultät: | M - Medizinische Fakultät |
Fachrichtung: | M - Innere Medizin |
Professur: | M - Prof. Dr. Michael Böhm M - Dr. med. Dr. sc.nat. Timo Speer |
Sammlung: | SciDok - Der Wissenschaftsserver der Universität des Saarlandes |
Dateien zu diesem Datensatz:
Datei | Beschreibung | Größe | Format | |
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biomedicines-10-00420.pdf | 1,41 MB | Adobe PDF | Öffnen/Anzeigen |
Diese Ressource wurde unter folgender Copyright-Bestimmung veröffentlicht: Lizenz von Creative Commons