Dataset Information

Chemokine CCL9 Is Upregulated Early in Chronic Kidney Disease and Counteracts Kidney Inflammation and Fibrosis.

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.

SUBMITTER: Hemmers C

PROVIDER: S-EPMC8962359 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Chemokine CCL9 Is Upregulated Early in Chronic Kidney Disease and Counteracts Kidney Inflammation and Fibrosis.

Hemmers Christian C Schulte Corinna C Wollenhaupt Julia J Wong Dickson W L DWL Harlacher Eva E Orth-Alampour Setareh S Klinkhammer Barbara Mara BM Schirmer Stephan H SH Böhm Michael M Marx Nikolaus N Speer Thimoteus T Boor Peter P Jankowski Joachim J Noels Heidi H

Biomedicines 20220210 2

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 ...[more]

PMID: 35203629

Similar Datasets

Project description:Interventions: All eligible participants will receive an imunochemical faecal occult blood test (IFOBT) kit (EIKEN brand) containing the test and instructions, with additional explanation provided by study staff, as required. A sample is then collected from two separate bowel motions. All samples will be self-collected. All completed kits will be sent and processed in a designated central laboratory and analysed according to the company’s standardised specifications. The results of this test can be positive, negative or inconclusive. All results will be sent via mail to the corresponding treating physicians, the participants and the research assistants at the Centre for Kidney Research. The screen is considered positive when one of the samples contains at least 50ng/ml of haemoglobin. Negative results are not followed up in the study but these patients are advised to continue with annual screening with their health practitioner. If the results are inconclusive, the participants will be contacted by phone and asked to repeat the test. Only participants with positive IFOBT findings will be referred for a diagnostic colonoscopy at a designated colonoscopic service. Study staff will track participants with positive IFOBT results and will ensure the referral process is scheduled effectively and efficiently for a colonoscopy. The participants will not be required to pay for the IFOBT kit or the diagnostic colonoscopy. Other clinical significant pathologies such as polyps, adenomas, vascular lesions will be documented and recorded. Wherever possible, they will be resected and sent for pathology. Depending upon the stage of initial diagnosis, further treatment may be required for participants with malignant polyps and cancers. All cancer diagnoses, including stage, histologica Primary outcome(s): Prevalence of a positive screening result (defined as positive IFOBT with at least one of the two stool samples containing at least 50ng/ml of haemoglobin) in people with chronic kidney disease in stages 3-5, dialysis and kidney transplant populations using the immunochemical faecal occult blood test. [Five years];Prevalence of colorectal cancer as determined with diagnostic colonoscopy, in people with chronic kidney disease in stages 3-5, dialysis and kidney transplant populations.[Five years];Test performance characteristics of immunochemical faecal occult blood screening, including: test specificity, positive predictive values and negative predictive value for colorectal cancers. [Five years] Study Design: Purpose: Diagnosis; Allocation: Non-randomised trial; Masking: Open (masking not used);Assignment: Single group;Type of endpoint: Safety/efficacy

Dataset Information

Chemokine CCL9 Is Upregulated Early in Chronic Kidney Disease and Counteracts Kidney Inflammation and Fibrosis.

Publications

Chemokine CCL9 Is Upregulated Early in Chronic Kidney Disease and Counteracts Kidney Inflammation and Fibrosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets