Early proinflammatory activation of renal tubular cells by normal and pathologic IgG.
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.
Ronda
Nicoletta
N
Department of Internal Medicine, Nephrology and Health Sciences, Università degli Studi di Parma, Italy. nicoletta.ronda@unipr.it
Cravedi
Paolo
P
Benozzi
Luisa
L
Lunghi
Paolo
P
Bonati
Antonio
A
Allegri
Landino
L
Carnevali
M Luisa
ML
Caserta
Caterina
C
Borghetti
Alberico
A
Buzio
Carlo
C
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
D001323:Autoantibodies; D007074:Immunoglobulin G; D015850:Interleukin-6; D048049:Extracellular Signal-Regulated MAP Kinases