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Original Paper

Early Proinflammatory Activation of Renal Tubular Cells by Normal and Pathologic IgG

Ronda N.a · Cravedi P.a · Benozzi L.a · Lunghi P.b · Bonati A.b · Allegri L.a · Carnevali M.L.a · Caserta C.a · Borghetti A.a · Buzio C.a

Author affiliations

aDepartment of Internal Medicine, Nephrology and Health Sciences and bDepartment of Clinical Sciences, Section of Hemato-Oncology, Università degli Studi di Parma, Italy

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Nephron Exp Nephrol 2005;100:e77–e84

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: November 29, 2002
Accepted: November 02, 2004
Published online: March 18, 2005
Issue release date: June 2005

Number of Print Pages: 1
Number of Figures: 6
Number of Tables: 1


eISSN: 1660-2129 (Online)

For additional information: https://www.karger.com/NEE

Abstract

Background/Aims: 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. Conclusion: 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.

© 2005 S. Karger AG, Basel


References

  1. Healy EB, Hugh R: Role of tubule epithelial cells in the pathogenesis of tubulointerstitial fibrosis induced by glomerular disease. Curr Opin Nephrol Hypertens 1998;7:525–530.
  2. Remuzzi G, Bertani T: Pathophysiology of progressive nephropathies. N Engl J Med 1998;339:1448–1456.
  3. Abbate M, Zoja C, Rottoli D, Corna D, Tomasoni S, Remuzzi G: Proximal tubular cells promote fibrogenesis by TGFβ1-mediated induction of peritubular myofibroblasts. Kidney Int 2002;61:2066–2077.
  4. Palmer BF: The renal tubule in the progression of chronic renal failure. J Invest Med 1997;45:346–361.
  5. Tang S, Sheerin NS, Zhou W, Brown Z, Sacks SH: Apical proteins stimulate complement synthesis by cultured human proximal tubular epithelial cells. J Am Soc Nephrol 1999;10:69–76.
  6. Burton CJ, Combe C, Walls J, Harris KPG: Fibronectin production by human tubular cells: the effect of apical protein. Kidney Int 1996;50:760–767.
  7. Zoja C, Morigi M, Figliuzzi M, et al: Proximal tubular cell synthesis and secretion of endothelin-1 on challenge with albumin and other proteins. Am J Kidney Dis 1995;26:934–941.
  8. Zoja C, Donadelli R, Colleoni S, et al: Protein overload stimulates RANTES production by proximal tubular cells depending on NF-kB activation. Kidney Int 1998;53:1608–1615.
  9. Morigi M, Macconi D, Zoja C, Donadelli R, Buelli S, Zanchi C, Ghilardi M, Remuzzi G: Protein overload-induced NF-kappaB activation in proximal tubular cells requires H(2)O(2) through a PKC-dependent pathway. J Am Soc Nephrol 2002;13:1179–1189.
  10. Detrisac CJ, Sens MA, Garvin AJ, Spicer SS, Sens DA: Tissue culture of human kidney epithelial cells of proximal tubule origin. Kidney Int 1984;25:383–390.
  11. Ronda N, Haury M, Nobrega A, Kaveri SV, Coutinho A, Kazatchkine MD: Analysis of natural and disease-associated autoantibody repertoires: Anti-endothelial cell IgG autoantibody activity in the serum of healthy individuals and patients with systemic lupus erythematosus. Int Immunol 1994;6:1651–1660.
  12. Neri TM, Carnevali L, Orlandini G, et al: Fluorescent in situ hybridization of tissue sections: A quantitative approach with confocal laser scanning microscopy. Eur J Hystochem 2000;44:193–198.
  13. Peruzzi L, Trusolino L, Amore A, et al: Tubulointerstitial responses in the progression of glomerular diseases. Albuminuria modulates avb5 integrin. Kidney Int 1996;50:1310–1320.
  14. Noronha IL, Niemir Z, Stein H, Waldherr R: Cytokines and growth factors in renal disease. Nephrol Dial Transplant 1995;10:775–786.
  15. Davies M, Martin J, Thomas GJ, Lovett DH: Proteinases and glomerular matrix turnover. Kidney Int 1992;41:671–678.
  16. Ranieri E, Gesualdo L, Petrarulo F, Schena F: Urinary IL-6/EGF ratio: a useful prognostic marker for the progression of renal damage in IgA nephropathy. Kidney Int 1996;50:1990–2001.
  17. Leonard M, Ryan MP, Watson AJ, Healy E: Possible signalling pathways involved in interleukin-6 (IL-6) production by human mesangial and proximal tubular cells. J Am Soc Nephrol 1997;8:442A.
  18. Abbate M, Zoja C, Corna D, Capitanio M, Bertani T, Remuzzi G: In progressive nephropathies, overload of tubular cells with filtered proteins translates glomerular permeability dysfunction into cellular signals of interstitial inflammation. J Am Soc Nephrol 1998;9:1213–1224.
  19. Burton CJ, Combe C, Walls J, Harris KP: Secretion of chemokines and cytokines by human tubular epithelial cells in response to proteins. Nephrol Dial Transplant 1999;14:2628–2633.
  20. Wang Y, Chen J, Chen L, Tay YC, Rangan GK, Harris DC: Induction of monocyte chemoattractant protein 1 in proximal tubular cells by urinary protein. J Am Soc Nephrol 1997;8:1537–1545.
  21. Ronda N, Gatti R, Orlandini G, Borghetti A: Binding and internalization of human IgG by living cultured endothelial cells. Clin Exp Immunol 1997;109:211–216.

Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: November 29, 2002
Accepted: November 02, 2004
Published online: March 18, 2005
Issue release date: June 2005

Number of Print Pages: 1
Number of Figures: 6
Number of Tables: 1


eISSN: 1660-2129 (Online)

For additional information: https://www.karger.com/NEE


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