Regulation and expression of chemokines: Potential role in glomerulonephritis

Glomerular diseases represent the major cause of renal failure, Despite decades of research our understanding of the mechanism(s) associated with immune-mediated glomerular injury remains poor, Consequently most of the therapies that are used are nonspecific with major side effects and offer minimal therapeutic benefits for the patient, The need for new strategies for therapy is clear, The drawing of leukocytes from the circulation into the inflamed glomerulus, accompanied by proliferation of resident mesangial cells and expansion of the mesangial matrix are key processes in the pathogenesis of glomerulonephritis (GN), The migration of inflammatory cells into an extravascular site requires a series of coordinated signals including the generation of a chemotactic gradient by the cells of the extravascular compartment, The nature of the stimulus and the subsequent spectrum of chemotactic: factors produced determine the specific leukocyte population recruited to the inflammatory site, Members of the chemokine family play a central role in this process by attracting and stimulating specific subsets of leukocytes, Our hypothesis is that mesangial cell-derived chemokines are responsible for the initiation and maintenance of glomerular inflammation; in this review we discuss our recent findings supporting this theory, Increasing our understanding of the intracellular pathways that regulate chemokine production in human mesangial cells may provide leads to the design of more effective therapies for the prevention and treatment of glomerular inflammation.