Open Access
Article
The role of chemokines in progressive renal disease
Carla Zoja1,Pablo Bautista Garcia1,Giuseppe Remuzzi1
1
Mario Negri Institute for Pharmacological Research, via Gavazzeni 11, 24125 Bergamo, Italy. zoja@marionegri.it
DOI: 10.2741/3343 Volume 14 Issue 5, pp.1815-1822
Published: 01 January 2009
Abstract

Tubulointerstitial damage followed by scarring and progressive loss of renal function is common to many forms of chronic proteinuric nephropathies. The severity of tubulointerstitial injury and in particular interstitial macrophage infiltration strongly correlate with the risk of renal failure. Proteins filtered through the glomerular capillary in excessive amount activate proximal tubular cells to upregulate chemokines mainly via activation of NF-kappaB-dependent pathway. Chemokines secreted toward the basolateral compartment of tubular epithelial cells incite local recruitment of mononuclear cells, that in turn interact with resident renal cells and extracellular matrix to create a proinflammatory microenvironment that amplifies tubulointerstitial inflammation and promotes renal scarring. The association between proteinuria and interstitial accumulation of inflammatory cells via activation of transcription factors and overexpression of chemokines has been established both experimentally and in human proteinuric nephropathies. Blocking leukocyte recruitment by interfering with transcription factor activity or chemokines and their receptors is envisioned as a strategy to retard kidney disease progression.

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Carla Zoja, Pablo Bautista Garcia, Giuseppe Remuzzi. The role of chemokines in progressive renal disease. Frontiers in Bioscience-Landmark. 2009. 14(5); 1815-1822.