Chemokines as therapeutic targets in renal disease.
Increased understanding of the fundamental importance of the role of chemokines and their receptors in inflammation, together with the demonstration of their involvement in human and experimental inflammatory renal disease, make these molecules potential therapeutic targets. A number of recent studies using genetically deficient mice and chemokine receptor antagonists in animal models have demonstrated that chemokine inhibition can attenuate experimental renal injury. Because there is simultaneous expression of multiple chemokines and receptors in disease, strategies that are aimed at antagonizing multiple chemokines receptor interactions are likely to be more effective than therapies that target a single chemokine. It is also now recognized that chemokines are involved in normal immune development and immune regulation. These observations, together with the results of studies that have demonstrated deleterious effects of chemokine receptor antagonism in experimental renal disease, highlight the need for thorough understanding of the role of individual chemokines in the pathogenesis of different types of renal disease before optimal therapeutic interventions may be achieved.
Holdsworth
S R
SR
Monash University Department of Medicine, Monash Medical Centre, Victoria, Australia. steven.holdsworth@med.monash.edu.au
Kitching
A R
AR
Tipping
P G
PG
D016263:AIDS-Associated Nephropathy / Q000276:immunology; D000818:Animals; D018932:Chemokine CCL2 / Q000502:physiology; D054428:Chemokine CX3CL1; D018925:Chemokines / Q000502:physiology*; D020523:Chemokines, CX3C; D019743:Chemokines, CXC / Q000502:physiology; D005921:Glomerulonephritis / Q000188:drug therapy; D006801:Humans; D007674:Kidney Diseases / Q000188:drug therapy* / Q000276:immunology; D016030:Kidney Transplantation / Q000276:immunology; D008565:Membrane Proteins / Q000502:physiology; D051379:Mice; D054389:Receptors, CCR1; D019707:Receptors, Chemokine / Q000502:physiology
C515300:CCR1 protein, human; C515538:CX3CL1 protein, human; C515301:Ccr1 protein, mouse; D018932:Chemokine CCL2; D054428:Chemokine CX3CL1; D018925:Chemokines; D020523:Chemokines, CX3C; D019743:Chemokines, CXC; C515539:Cx3cl1 protein, mouse; D008565:Membrane Proteins; D054389:Receptors, CCR1; D019707:Receptors, Chemokine