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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

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