Inflammation Research

, Volume 62, Issue 1, pp 45–52 | Cite as

Effect of tonsillar mononuclear cell supernatants in patients with IgA nephropathy on renal tubular epithelial cells

  • Youzhou Tang
  • Youming Peng
  • Sha Yang
  • Hong Liu
  • Gang Wu
  • Fuyou Liu
Original Research Paper



This study aimed to investigate the immunological relationship and the mechanism between tonsillar inflammation and immunoglobulin A nephropathy (IgAN).


Tonsillar mononuclear cells (TMCs) were prepared from 13 patients with IgAN and 13 patients with chronic tonsillitis but without renal disease. The human renal tubular epithelial cell (TEC) line, HK-2, was used to test the effects of secretions from the TMCs.


Phytohemagglutinin (PHA) was used to induce the inflammatory responses in TMCs. The secretions from TMCs, stimulated with or without PHA, were collected and applied to HK-2 cells. The proliferation, apoptosis, and epithelial–mesenchymal transition (EMT) of HK-2 cells were evaluated. The expression of key components during apoptosis and EMT was measured.


The secretions from PHA-stimulated IgAN TMCs significantly inhibited proliferation, promoted apoptosis, and down-regulated Bcl-2 in HK-2 cells (P < 0.05) in time- and concentration-dependent manners. They also modulated the expression of key components during EMT, E-cadherin and α-SMA (P < 0.05).


The secretions from PHA-stimulated IgAN TMCs can cause the inhibition of proliferation, promotion of apoptosis, down-regulation of Bcl-2, and EMT effects in HK-2 TECs, which may reflect the in-vivo remote modulation of functions of renal TECs by tonsillar inflammation.


IgAN TMCs TECs Apoptosis EMT 



We thank Dr. Shousong Cao and Dr. Meir Wetzler of Roswell Park Cancer Institute (Buffalo, NY, USA) for proofreading the manuscript and for their invaluable suggestions.


  1. 1.
    Tomino Y, Endoh M, Nomoto Y, Sakai H. Immunoglobulin A1 and IgA nephropathy. N Engl J Med. 1981;305:1159–60.PubMedCrossRefGoogle Scholar
  2. 2.
    Nishi S. The prognosis of IgA nephropathy–favorable or poor? Intern Med. 2001;40:679–80.PubMedCrossRefGoogle Scholar
  3. 3.
    Kobayashi Y, Tateno S, Hiki Y, Shigematsu H. IgA nephropathy: prognostic significance of proteinuria and histological alterations. Nephron. 1983;34:146–53.PubMedCrossRefGoogle Scholar
  4. 4.
    Feehally J, Beattie TJ, Brenchley PEC, Coupes BM, Mallick NP, Postlethwaite RJ. Sequential study of the IgA system in relapsing IgA nephropathy. Kidney Int. 1986;30:924–31.PubMedCrossRefGoogle Scholar
  5. 5.
    Emancipator SN, Gallo GR, Lamm ME. Experimental IgA nephropathy induced by oral immunization. J Exp Med. 1983;157:572–82.PubMedCrossRefGoogle Scholar
  6. 6.
    Kodama S, Suzuki M, Arita M, Mogi G. Increase in tonsillar germinal centre B-1 cell numbers in IgA nephropathy (IgAN) patients and reduced susceptibility to Fas-mediated apoptosis. Clin Exp Immunol. 2001;123:301–8.PubMedCrossRefGoogle Scholar
  7. 7.
    Inoue T, Sugiyama H, Kikumoto Y, et al. Downregulation of the beta1,3- galactosyltransferase gene in tonsillar B lymphocytes and aberrant lectin bindings to tonsillar IgA as a pathogenesis of IgA nephropathy. Contrib Nephrol. 2007;157:120–4.PubMedGoogle Scholar
  8. 8.
    Liu H, Peng Y, Liu F, Xiao W, Zhang Y, Li W. Expression of IgA class switching gene in tonsillar mononuclear cells in patients with IgA nephropathy. Inflamm Res. 2011;60:869–78.PubMedCrossRefGoogle Scholar
  9. 9.
    Tokuda M, Shimizu J, Sugiyama N, et al. Direct evidence of the production of IgA by tonsillar lymphocytes and the binding of IgA to the glomerular mesangium of IgA nephropathy patients. Acta Otolaryngol. 1996;523 Suppl:182–4.Google Scholar
  10. 10.
    Hiki Y, Horie A, Yasuda Y, Iwase H, Sugiyama S. IgA nephropathy and tonsils–an approach from the structure of IgA1 produced by tonsillar lymphocytes. Acta Otolaryngol. 2004;555 Suppl:28–31.Google Scholar
  11. 11.
    Sato M, Hotta O, Tomioka S, et al. Cohort study of advanced IgA nephropathy: efficacy and limitations of corticosteroids with tonsillectomy. Nephron Clin Pract. 2003;93:137–45.CrossRefGoogle Scholar
  12. 12.
    Huang H. Relationship between the Pathogenesis of IgA Nephropathy and the Palatine Tonsils. Ph. D. Dissertation, Central South University, Changsha, China. 2007.Google Scholar
  13. 13.
    Lee TW, Park JK, Ahn JH, Ihm CG, Kim MJ. Role of mononuclear cells of IgA nephropathy on ICAM-1 expression in mesangial cells. Korean J Intern Med. 1998;13:27–32.PubMedGoogle Scholar
  14. 14.
    Lee TW, Ahn JH, Park JK, Ihm CG, Kim MJ. Tumor necrosis factor alpha from peripheral blood mononuclear cells of IgA nephropathy and mesangial cell proliferation. Korean J Intern Med. 1994;9:1–8.PubMedGoogle Scholar
  15. 15.
    Ichinohe S, Hussain IR, Johnston SL. Cytokine production of RSV/PHA-stimulated tonsillar mononuclear cells: influences of age and atopy. Eur Respir J. 2003;22:317–22.PubMedCrossRefGoogle Scholar
  16. 16.
    Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983;65:55–63.PubMedCrossRefGoogle Scholar
  17. 17.
    Thiagarajan P, Tait JF. Binding of annexin V/placental anticoagulant protein I to platelets. Evidence for phosphatidylserine exposure in the procoagulant response of activated platelets. J Biol Chem. 1990;265:17420–3.PubMedGoogle Scholar
  18. 18.
    Dachary PJ, Freyssinet JM, Pasquet JM, Carron JC, Nurden AT. Annexin V as a probe of aminophospholipid exposure and platelet membrane vesiculation: a flow cytometry study showing a role for free sulfhydryl groups. Blood. 1993;81:2554–65.Google Scholar
  19. 19.
    Korsmeyer SJ, Shutter JR, Veis DJ, Merry DE, Oltvai ZN. Bcl-2/Bax: a rheostat that regulates an anti-oxidant pathway and cell death. Semin Cancer Biol. 1993;4:327–32.PubMedGoogle Scholar
  20. 20.
    Reed JC, Miyashita T, Krajewski S, et al. Bcl-2 family proteins and the regulation of programmed cell death in leukemia and lymphoma. Cancer Treat Res. 1996;84:31–72.PubMedCrossRefGoogle Scholar
  21. 21.
    Kuki K, Gotoh H, Hayashi M, et al. Immunity of tonsil and IgA nephropathy—relationship between IgA nephropathy and tonsillitis. Acta Otolaryngol. 2004;555 Suppl:6–9.Google Scholar
  22. 22.
    Fujieda S, Suzuki S, Sunaga H, et al. Induction of IgA against Haemophilus parainfluenzae antigens in tonsillar mononuclear cells from patients with IgA nephropathy. Clin Immunol. 2000;95:235–43.PubMedCrossRefGoogle Scholar
  23. 23.
    Fujieda S, Suzuki S, Sunaga H, et al. Production of interferon-gamma by tonsillar mononuclear cells in IgA nephropathy patients. Acta Otolaryngol. 2000;120:649–54.PubMedCrossRefGoogle Scholar
  24. 24.
    Zheng L, Sinniah R, Hsu SIH. Renal cell apoptosis and proliferation may be linked to nuclear factor-kappaB activation and expression of inducible nitric oxide synthase in patients with lupus nephritis. Hum Pathol. 2006;37:637–47.PubMedCrossRefGoogle Scholar
  25. 25.
    Devarajan P. Cellular and molecular derangements in acute tubular necrosis. Curr Opin Pediatr. 2005;17:193–9.PubMedCrossRefGoogle Scholar
  26. 26.
    Isaka Y, Suzuki C, Abe T, et al. Bcl-2 protects tubular epithelial cells from ischemia/reperfusion injury by dual mechanisms. Transplant Proc. 2009;41:52–4.PubMedCrossRefGoogle Scholar
  27. 27.
    Korsmeyer SJ. BCL-2 gene family and the regulation of programmed cell death. Cancer Res. 1999;59:1693–700.Google Scholar
  28. 28.
    Chevalier RL, Kim A, Thornhill BA, Wolstenholme JT. Recovery following relief of unilateral ureteral obstruction in the neonatal rat. Kidney Int. 1999;55:793–807.PubMedCrossRefGoogle Scholar
  29. 29.
    Bogenschutz O, Bohle A, Batz C, et al. IgA nephritis: on the importance of morphological and clinical parameters in the long-term prognosis of 239 patients. Am J Nephrol. 1990;10:137–47.PubMedCrossRefGoogle Scholar
  30. 30.
    Strutz F, Okada H, Lo CW, Danoff T, Carone RL, Tomaszewski JE, Neilson EG. Identification and characterization of a fibroblast marker: FSP1. J Cell Biol. 1995;130:393–405.PubMedCrossRefGoogle Scholar
  31. 31.
    Zeisberg M, Kalluri R. The role of epithelial-to-mesenchymal transition in renal fibrosis. J Mol Med. 2004;82:175–81.PubMedCrossRefGoogle Scholar
  32. 32.
    Huang H, Peng Y, Liu F, Lei H. Is IgA nephropathy induced by abnormalities of CD4 + CD25 + Treg cells in the tonsils? Med Hypotheses. 2007;69:410–3.PubMedCrossRefGoogle Scholar
  33. 33.
    Yang J, Liu Y. Dissection of key events in tubular epithelial to myofibroblast transition and its implications in renal interstitial fibrosis. Am J Pathol. 2001;159:1465–75.PubMedCrossRefGoogle Scholar
  34. 34.
    Zavadil J, Bottinger EP. TGF-beta and epithelial-to-mesenchymal transitions. Oncogene. 2005;24:5764–74.PubMedCrossRefGoogle Scholar
  35. 35.
    Kawaguchi M, Sakai T, Sakamaki A, et al. Expanded primary T nodules in the palatine tonsils from patients with IgA nephropathy. Acta Otolaryngol. 1993;508 Suppl:36–42.Google Scholar
  36. 36.
    Bene MC, Faure G. Hurault de Ligny B, et al. Immunoglobulin A nephropathy. Quantitative immunohistomorphometry of the tonsillar plasma cells evidences an inversion of the immunoglobulin A versus immunoglobulin G secreting cell balance. J Clin Invest. 1983;71:1342–7.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Basel AG 2012

Authors and Affiliations

  • Youzhou Tang
    • 1
    • 2
  • Youming Peng
    • 1
    • 2
    • 3
  • Sha Yang
    • 1
    • 2
  • Hong Liu
    • 1
    • 2
  • Gang Wu
    • 1
    • 2
  • Fuyou Liu
    • 1
    • 2
  1. 1.Department of NephrologyThe Second Xiangya Hospital, Central South UniversityChangshaPeople’s Republic of China
  2. 2.Institute of NephrologyThe Second Xiangya Hospital, Central South UniversityChangshaPeople’s Republic of China
  3. 3.ChangshaPeople’s Republic of China

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