Nephrol Dial Transplant (2003) 18: 36-45
© 2003 European Renal Association-European Dialysis and Transplant Association
Polymeric IgA increases the synthesis of macrophage migration inhibitory factor by human mesangial cells in IgA nephropathy
Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong
Background. It has been suggested that polymeric IgA (pIgA) or IgA immune complexes play a significant pathogenic role in IgA nephropathy (IgAN). Macrophage migration inhibitory factor (MIF) shares many activities with other pro-inflammatory cytokines. In human glomerulonephritis, including IgAN, glomerular expression of MIF is found to correlate with progressive renal injury. We hypothesized that deposition of pIgA within the kidney may lead to enhanced synthesis of MIF by mesangial cells.
Methods. In this study we examined the effect of pIgA and monomeric IgA (mIgA) from randomly selected patients with IgAN in clinical quiescence on the gene expression and protein synthesis of MIF in cultured human mesangial cells (HMC).
Results. Both pIgA and mIgA from IgAN patients or matched healthy controls increased MIF gene expression and protein synthesis in a dose-dependent fashion. The magnitude of MIF protein induction by pIgA (100 µg/ml) was similar to that of tumour necrosis factor-
(TNF-) at 10 pg/ml. In all subjects, the induction of MIF was higher for pIgA when compared with mIgA (P<0.01). Furthermore, the up-regulation of MIF synthesis by either pIgA or mIgA was significantly higher in IgAN patients than in healthy controls (P<0.05). Similarly, pIgA and mIgA were able to induce TNF- gene expression and protein synthesis in mesangial cells. Incubation of mesangial cells with neutralizing antibody to TNF- reduced the MIF synthesis induced by pIgA.
Conclusion. We demonstrate that pIgA is capable of inducing MIF and TNF- production in HMC, which may play a major pathogenic role in IgAN. Induction of MIF can be partially blocked by neutralizing antibody to TNF-, suggesting the possibility that up-regulation of MIF synthesis in HMC is mediated via an amplifying proinflammatory loop involving TNF-.
Keywords: IgA nephropathy; IgA1; macrophage migration inhibitory factor; mesangial cells; polymeric IgA; tumour necrosis factor-
Correspondence and offprint requests to: Professor K. N. Lai, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong. Email: knlai{at}hkucc.hku.hk
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. C. K. Leung, S. C. W. Tang, L. Y. Y. Chan, W. L. Chan, and K. N. Lai Synthesis of TNF-{alpha} by mesangial cells cultured with polymeric anionic IgA role of MAPK and NF-{kappa}B Nephrol. Dial. Transplant., January 1, 2008; 23(1): 72 - 81. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. D. Oortwijn, A. Roos, L. Royle, D. J. van Gijlswijk-Janssen, M. C. Faber-Krol, J.-W. Eijgenraam, R. A. Dwek, M. R. Daha, P. M. Rudd, and C. van Kooten Differential Glycosylation of Polymeric and Monomeric IgA: A Possible Role in Glomerular Inflammation in IgA Nephropathy J. Am. Soc. Nephrol., December 1, 2006; 17(12): 3529 - 3539. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. C. Smith, K. Molyneux, J. Feehally, and J. Barratt O-Glycosylation of Serum IgA1 Antibodies against Mucosal and Systemic Antigens in IgA Nephropathy J. Am. Soc. Nephrol., December 1, 2006; 17(12): 3520 - 3528. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Y.Y. Chan, J. C.K. Leung, S. C.W. Tang, C. B.Y. Choy, and K. N. Lai Tubular Expression of Angiotensin II Receptors and Their Regulation in IgA Nephropathy J. Am. Soc. Nephrol., August 1, 2005; 16(8): 2306 - 2317. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. K. Leung, L. Y. Y. Chan, A. W. L. Tsang, E. W. L. Liu, M. F. Lam, S. C. W. Tang, and K. N. Lai Anti-macrophage migration inhibitory factor reduces transforming growth factor-{beta}1 expression in experimental IgA nephropathy Nephrol. Dial. Transplant., August 1, 2004; 19(8): 1976 - 1985. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. N. Lai, S. C. W. Tang, J.-Y. Guh, T.-D. Chuang, M. F. Lam, L. Y. Y. Chan, A. W. L. Tsang, and J. C. K. Leung Polymeric IgA1 from Patients with IgA Nephropathy Upregulates Transforming Growth Factor-{beta} Synthesis and Signal Transduction in Human Mesangial Cells via the Renin-Angiotensin System J. Am. Soc. Nephrol., December 1, 2003; 14(12): 3127 - 3137. [Abstract] [Full Text] [PDF]
|
|