title: Resident kidney cells and their involvement in glomerulonephritis.
abstract: Each year, worldwide, there is an increasing number of patients with chronic kidney disease that progress to end-stage renal disease. Glomerulonephritis (GN) is the commonest single cause of end-stage renal failure in the world. GN can be a manifestation of primary renal injury or may be a secondary feature of a systemic disease process, for example Systemic Lupus Erythematosus (SLE) and Anti-Neutrophilic Cytoplasmic Antibody (ANCA) associated vasculitis. Understanding of the immunopathogenesis of GN has advanced considerably over the last 25 years, particularly the immune system's role. The injurious role of infiltrating leukocytes and humoral mediators has been emphasised, however, the contribution of intrinsic renal cells has proved difficult to define. Most evidence for the pro-inflammatory capacity of intrinsic renal cells has been derived from in vitro studies. Although cytokine production by intrinsic renal cells has been demonstrated by immunohistochemistry and in situ hybridisation studies in renal tissue during the development of GN, the functional contribution of this cytokine production to renal injury was unknown. Little was known about direct and specific interactions between different glomerular cell types and infiltrating leukocytes in the pathogenesis of GN. The development of mice with genetic deficiencies of pro-inflammatory mediators and cytokines, and the technique of bone marrow transplantation into irradiated recipients to produce chimeric mice with restricted cytokine expression has allowed in vivo assessment of the functional contribution made by intrinsic renal cells. Studies have demonstrated the significant contribution of intrinsic renal cell derived cytokines (e.g. TNF) in mediating GN, whereas others (IL-1beta) have a relatively minor role.
authors.affiliation: Centre for Inflammatory Diseases, Monash University, Department of Medicine, Monash Medical Centre, Clayton, Victoria 3168, Australia. Jennifer.timoshanko@med.monash.edu.au
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Timoshanko
authors.forename: Peter G
authors.initials: PG
authors.lastname: Tipping
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000502:physiology; D018925:Chemokines / Q000502:physiology; D005921:Glomerulonephritis / Q000473:pathology*; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology; D007668:Kidney / Q000473:pathology*; D007678:Kidney Glomerulus / Q000473:pathology; D013601:T-Lymphocytes / Q000473:pathology / Q000502:physiology; D018417:Th1 Cells / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D015815:Cell Adhesion Molecules; D018925:Chemokines; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha