title: Podocytes express IL-6 and lipocalin 2/ neutrophil gelatinase-associated lipocalin in lipopolysaccharide-induced acute glomerular injury.
abstract: OBJECTIVE
  Acute kidney injury (AKI) contributes to significant morbidity and mortality in the intensive care unit (ICU). Plasma levels of interleukin (IL)-6 predict the development of AKI and are associated with higher mortality in ICU patients with AKI. Most studies in AKI have focused on the tubulo-interstitium, despite evidence of glomerular involvement. In the following study, our goals were to investigate the expression of IL-6 and its downstream mediators in septic-induced AKI.
  
  
  METHODS
  Podocytes were treated in vitro with lipopolysaccharide (LPS) and mice were treated with LPS, and we evaluated IL-6 expression by real-time PCR, ELISA and in situ RNA hybridization.
  
  
  RESULTS
  Following LPS stimulation, IL-6 is rapidly and highly induced in cultured podocytes and in vivo in glomeruli and infiltrating leukocytes. Surprisingly, in direct response to exogenous IL-6, podocytes produce lipocalin-2/neutrophil gelatinase-associated lipocalin (Lcn2/Ngal). LPS also potently induces Lcn2/Ngal expression in podocytes in culture and in glomeruli in vivo. Intense Lcn2/Ngal expression is also observed in IL-6 knockout mice, suggesting that while IL-6 may be sufficient to induce glomerular Lcn2/Ngal expression, it is not essential.
  
  
  CONCLUSIONS
  The glomerulus is involved in septic AKI, and we demonstrate that podocytes secrete key mediators of AKI including IL-6 and Lcn2/Ngal.
authors.affiliation: Research Service and Division of Nephrology-Hypertension, Veterans Affairs San Diego Healthcare System, Veterans Medical Research Foundation, San Diego, CA 92161, USA.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Lee
authors.forename: Emily
authors.initials: E
authors.lastname: Borsting
authors.forename: Anne-Emilie
authors.initials: AE
authors.lastname: Declèves
authors.forename: Prabhleen
authors.initials: P
authors.lastname: Singh
authors.forename: Robyn
authors.initials: R
authors.lastname: Cunard
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D000209:Acute-Phase Proteins / Q000096:biosynthesis* / Q000378:metabolism; D000818:Animals; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000378:metabolism; D007678:Kidney Glomerulus / Q000378:metabolism*; D000071068:Lipocalin-2; D054834:Lipocalins / Q000096:biosynthesis* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015513:Oncogene Proteins / Q000096:biosynthesis* / Q000378:metabolism; D050199:Podocytes / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000209:Acute-Phase Proteins; D015850:Interleukin-6; D000071068:Lipocalin-2; D054834:Lipocalins; D008070:Lipopolysaccharides; D015513:Oncogene Proteins; C577686:interleukin-6, mouse; C071332:Lcn2 protein, mouse