Figure 1: The inflammatory amplification loop in the diabetic kidney. Circulating immune cells such as monocytes are recruited into the diabetic kidney due to upregulation of adhesion molecules such as ICAM-1. Chemokines such as MCP-1 act as chemoattractants which promote accumulation of the immune cells in the kidney. These immune cells are activated by numerous signals such as the ligation of c-fms by CSF-1, receptor for AGE by AGEs, and the Fcγ receptors by antioxidized LDL immune complexes. CSF-1 also promotes the maturation, proliferation, and survival of monocyte-macrophages. Activated immune cells act as inflammatory cells and elaborate proinflammatory cytokines and reactive oxygen species (ROS), which trigger a cell signalling cascade mediated by the stress-activated protein kinases, p38 MAPK, and JNK. These kidney cells then respond by the production of chemokines such as MCP-1 and CSF-1, and profibrotic factors such as TGF- which increase extracellular matrix production by mesangial cells and interstitial fibroblasts. Ultimately, there is cellular injury and progressive fibrosis within the diabetic kidney.