Chemokine CCL9 Is Upregulated Early in Chronic Kidney Disease and Counteracts Kidney Inflammation and Fibrosis
CCL6; CCL9; MIP-1γ; chemokine; chronic kidney disease; collagen; fibrosis; inflammation; macrophage.- Biomedicines
- 4.7
- 2022 Feb 10;10(2):420.
- Mouse
- 抗体芯片
- 免疫/内分泌
- 免疫/内分泌
- 单核细胞
- CCL11/Eotaxin,CCL6/C10,CXCL11/I-TAC,CCL12/MCP-5,CCL8/MCP-2,CXCL12/SDF-1,CCL2/JE/MCP-1,CCL9/10/MIP-1 gamma,CXCL13/BLC/BCA-1,CCL21/6Ckine,Chemerin,CXCL16,CCL22/MDC,Complement Component C5/C5a,CXCL2/MIP-2,CCL27/CTACK,CX3CL1/Fractalkine,CXCL9/MIG,CCL28,CXCL1/KC,IL-16,CCL3/CCL4 (MIP-1 alpha /MIP-1 beta),CXCL10/IP-10/CRG-2,LIX,CCL5/RANTES
相关货号
LXAM025-1
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.Keywords:CCL6; CCL9; MIP-1γ; chemokine; chronic kidney disease; collagen; fibrosis; inflammation; macrophage.
金课堂之文献解析 文献原文请点击
本网站销售的所有产品及服务均不得用于人类或动物之临床诊断或治疗,仅可用于工业或者科研等非医疗目的。