The role of chemokines and chemokine receptors in diabetic nephropathy.
Diabetic nephropathy is increasingly considered as an inflammatory disease characterized by leukocyte infiltration at every stage of renal involvement. Chemokines are important participators in the recruitment of specific subpopulations of inflammatory cells into renal compartments. MCP-1/CCL2 has been identified as having a key role in monocyte/macrophage recruitment in animal models of diabetic nephropathy, as well as in renal biopsies from patients with type 1 and 2 diabetes. Various factors of the diabetic milieu can induce renal expression of MCP-1/CCL2 and cell adhesion molecules, and thereby mediate the macrophage responses that ultimately cause renal injury. Possibly fractalkine/CX3CL1 functions as an arrest chemokine in monocyte/macrophage adhesion before migration into the kidney. T lymphocyte recruitment is influenced by up-regulation of RANTES/CCL5 throughout glomerular as well as tubulointerstitial structures as well as IP-10/CXCL10 mainly in the tubulointerstitium. Improved knowledge of gene polymorphisms of chemokines and their receptors could be useful to predict onset of diabetic nephropathy and define its progression. Blockade of the renin-angiotensin-aldosterone system is currently the only clinically used strategy to treat the inflammatory process in diabetic nephropathy. Newer strategies point to chemokine receptor antagonists and even to immunosuppressive therapy, but still remain in the experimental stage.
Ruster
Christiane
C
Friedrich Schiller University Jena, Department of Internal Medicine III, Erlanger Allee 101, D-07740 Jena, Germany.
Wolf
Gunter
G
D000818:Animals; D018932:Chemokine CCL2 / Q000378:metabolism; D054428:Chemokine CX3CL1 / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D008954:Models, Biological; D008957:Models, Genetic; D011110:Polymorphism, Genetic; D019707:Receptors, Chemokine / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism
C111835:CCL2 protein, human; C515538:CX3CL1 protein, human; D018932:Chemokine CCL2; D054428:Chemokine CX3CL1; D018925:Chemokines; D019707:Receptors, Chemokine