title: Early proinflammatory activation of renal tubular cells by normal and pathologic IgG.
abstract: OBJECTIVE
  To verify whether human IgG induces proinflammatory activation of human proximal tubular epithelial cells (PTEC) independent of the metabolic overload of protein reabsorption.
  
  
  METHODS
  Cultured PTEC were incubated with normal IgG, IgG from systemic lupus erythematosus (SLE) patients, albumin or transferrin. IL-6 secretion and extracellular regulated kinase (ERK) activation (dual-phosphorylated ERK) were measured by ELISA and by Western blotting of PTEC extracts, respectively; renal biopsy specimens from patients with IgG and non-IgG proteinuria were analyzed by immunohistochemistry and in situ hybridization to detect ERK-P and IL-6.
  
  
  RESULTS
  Normal and SLE IgG, but not albumin or transferrin, induced an early significant increase in IL-6 secretion by PTECs. Also ERK activation was found after 1-hour incubation of PTEC with IgG, but not with control medium and albumin-treated PTEC. Activated ERK and IL-6 were found to colocalize in tubular cells in the kidney specimens of patients with IgG proteinuria only.
  
  
  CONCLUSIONS
  IgG-dependent early activation of ERK and increased IL-6 secretion in PTEC suggest that IgG filtered during nonselective proteinuria may play a specific role in tubulointerstitial disease. Such a role could be particularly relevant in diseases associated with abnormal IgG pool compositions, such as SLE. Preliminary results on human renal biopsy specimens suggest that our in vitro observations may also be relevant in vivo.
authors.affiliation: Department of Internal Medicine, Nephrology and Health Sciences, Università degli Studi di Parma, Italy. nicoletta.ronda@unipr.it
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Ronda
authors.forename: Paolo
authors.initials: P
authors.lastname: Cravedi
authors.forename: Luisa
authors.initials: L
authors.lastname: Benozzi
authors.forename: Paolo
authors.initials: P
authors.lastname: Lunghi
authors.forename: Antonio
authors.initials: A
authors.lastname: Bonati
authors.forename: Landino
authors.initials: L
authors.lastname: Allegri
authors.forename: M Luisa
authors.initials: ML
authors.lastname: Carnevali
authors.forename: Caterina
authors.initials: C
authors.lastname: Caserta
authors.forename: Alberico
authors.initials: A
authors.lastname: Borghetti
authors.forename: Carlo
authors.initials: C
authors.lastname: Buzio
mesh_terms: D001323:Autoantibodies; D001706:Biopsy; D015153:Blotting, Western; D018929:Cell Culture Techniques; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007249:Inflammation; D015850:Interleukin-6 / Q000096:biosynthesis; D007684:Kidney Tubules / Q000276:immunology* / Q000473:pathology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D009395:Nephritis, Interstitial / Q000503:physiopathology*; D011507:Proteinuria
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; D015850:Interleukin-6; D048049:Extracellular Signal-Regulated MAP Kinases