ABB  Vol.2 No.1 , February 2011
The gene expression of NGAL and TLR9 in glomerulus and tubulo-interstitium of patients with lupus nephritis
Abstract: Background The role of neutrophil gelatinase associated lipocalin (NGAL) and Toll-like receptor 9 (TLR9) in the pathogenesis of lupus nephritis remain elusive. Methods We quantified the glomerular and tubulointerstitial mRNA expression of NGAL and TLR9 in 42 patients with lupus nephritis (LN group) and 10 controls. Results As compared to controls, LN group had higher glomerular expression of TLR9, and higher tubulointerstitial expression of NGAL and TLR9. Tubulointerstitial NGAL expression significantly correlated with proteinuria (r = 0.492; p = 0.003), renal function (r = -0.386; p = 0.022) and histological chronicity index (r = 0.540; p = 0.004). Proteinuria had significant correlation with glomerular (r = 0.554; p = 0.001) and tubulointerstitial (r = 0.379; p = 0.043) TLR9 expression. Furthermore, there was a significant difference in tubulointerstitial expression of NGAL between treatment response groups. Conclusion There is an increase in intra-renal mRNA expression of NGAL and TLR9 in LN. Although tubulointerstitial expression of NGAL does not correlate with systemic disease activity, it correlates with proteinuria, renal function, and therapeutic response. The role of NGAL in the pathogensis in LN, as well as its application as biomarker for lupus nephritis, requires further study.
Cite this paper: nullLu, J. , Kwan, B. , Lai, F. , Choi, P. , Tam, L. , Li, E. , Chow, K. , Wang, G. , Li, P. and Szeto, C. (2011) The gene expression of NGAL and TLR9 in glomerulus and tubulo-interstitium of patients with lupus nephritis. Advances in Bioscience and Biotechnology, 2, 33-39. doi: 10.4236/abb.2011.21006.

[1]   Lauwerys, B. and Houssiau, F. (1998) Cytokines: Clues to the pathogenesis of SLE. Lupus, 7, 211-213. doi:10.1191/096120398678920136

[2]   Karonitsch, T., Feierl, E., Steiner, C., et al. (2009) Activation of the interferon-gamma signaling pathway in systemic lupus erythematosus peripheral blood mono- nuclear cells. Arthritis Rheum, 60, 1463-1471. doi:10.1002/art.24449

[3]   Lee, H., Mima, T., Sugino, H., et al. (2009) Interactions among type I and type II interferon, tumor necrosis factor, and beta-estradiol in the regulation of immune response-related gene expressions in systemic lupus erythematosus. Arthritis Res Ther, 11, 1.

[4]   Kjeldsen, L., Bainton, D., Sengel?v, H., et al. (1994) Identification of neutrophil gelatinase-associated lipocalin as a novel matrix protein of specific granules in human neutrophils. Blood, 83, 799-807. doi:10.1080/00365510802150158

[5]   Devarajan, P. (2008) Neutrophil gelatinase-associated lipocalin (NGAL): A new marker of kidney disease. Scandinavian journal of clinical and laboratory investigation, 241, 89-94.

[6]   Pitashny, M., Schwartz, N., Qing, X., et al. (2007) Urinary lipocalin-2 is associated with renal disease activity in human lupus nephritis. Arthritis Rheum, 56, 1894-1903.

[7]   Nakano, S., Morimoto, S., Suzuki, J., et al. (2008) Role of pathogenic auto-antibody production by Toll-like receptor 9 of B cells in active systemic lupus erythe- matosus. Rheumatology, 47, 145-149.

[8]   Hemmi, H., Takeuchi, O., Kawai, T., et al. (2000) A Toll-like receptor recognizes bacterial DNA. Nature, 408, 740-745. doi:10.1038/35047123

[9]   Matsuo, S., Yamazaki, S., Takeshige, K., et al. (2007) Crucial roles of binding sites for NF-kappaB and C/EBPs in IkappaB-zeta-mediated transcriptional activation. Bio- chemical Journal, 405, 605-615. doi:10.1042/BJ20061797

[10]   Hochberg, M. (1997) Updating the American college of rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum, 40, 1725. doi:10.1002/art.1780400928

[11]   Bombardier, C., Gladman, D., Urowitz, M., et al. (1992) Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthritis Rheum, 35, 630-640.

[12]   Levey, A., Bosch, J., Lewis, J., et al. (1999) A more accurate method to estimate glomerular filtration rate from serum creatinine: A new prediction equation. Modification of diet in renal disease study group. Annals of Internal Medicine, 130, 461-470.

[13]   Weening, J., D'Agati, V., Schwartz, M., et al. (2004) The classification of glomerulonephritis in systemic lupus erythematosus revisited. Kidney International, 65, 521- 530. doi:10.1111/j.1523-1755.2004.00443.x

[14]   Chan, R., Lai, F., Li, E., et al. (2007) Intrarenal cytokine gene expression in lupus nephritis. Annals of the Rheumatic Diseases, 66, 886-892.

[15]   Wang, G., Lai, F., Lai, K., et al. (2009) Discrepancy between intrarenal messenger RNA and protein expression of ACE and ACE2 in human diabetic nephropathy. American Journal of Nephrology, 29, 524- 531. doi:10.1159/000185629

[16]   Chan, R., Lai, F., Li, E., et al. (2004) Expression of chemokine and fibrosing factor messenger RNA in the urinary sediment of patients with lupus nephritis. Arthritis Rheum, 50, 2882-2890.

[17]   Chan, T., Li, F., Tang, C., et al. (2000) Efficacy of mycophenolate mofetil in patients with diffuse proliferative lupus nephritis. Hong Kong-Guangzhou nephrology study group. The New England Journal of Medicine, 343, 1156-1162. doi:10.1056/NEJM200010193431604

[18]   Brunner, H., Mueller, M., Rutherford, C., et al. (2006) Urinary neutrophil gelatinase-associated lipocalin as a biomarker of nephritis in childhood-onset systemic lupus erythematosus. Arthritis Rheum, 54, 2577-2584. doi:10.1002/art.22008

[19]   Bolignano, D., Coppolino, G., Campo, S., et al. (2008) Urinary neutrophil gelatinase-associated lipocalin (NGAL) is associated with severity of renal disease in proteinuric patients. Nephrol Dial Transplant, 23, 414-416.

[20]   Hinze, C., Suzuki, M., Klein-Gitelman, M., et al. (2009) Neutrophil gelatinase-associated lipocalin is a predictor of the course of global and renal childhood-onset sys- temic lupus erythematosus disease activity. Arthritis Rheum, 60, 2772-2781. doi:10.1002/art.24751

[21]   Machida, H., Ito, S., Hirose, T., et al. (2010) Expression of Toll-like receptor 9 in renal podocytes in child- hood-onset active and inactive lupus nephritis. Nephrol Dial Transplant, 25, 2430-2537.

[22]   Benigni, A., Caroli, C., Longaretti, L., et al. (2007) Involvement of renal tubular Toll-like receptor 9 in the development of tubulointerstitial injury in systemic lupus. Arthritis Rheum, 56, 1569-1578.

[23]   Papadimitraki, E., Tzardi, M., Bertsias, G., et al. (2009) Glomerular expression of toll-like receptor-9 in lupus nephritis but not in normal kidneys: implications for the amplification of the inflammatory response. Lupus, 18, 831-835. doi:10.1177/0961203309103054

[24]   Leadbetter, E., Rifkin, I., Hohlbaum, A., et al. (2002) Chromatin-IgG complexes activate B cells by dual engagement of IgM and Toll-like receptors. Nature, 416, 603-607. doi:10.1038/416603a

[25]   Mortensen, E., Fenton, K. and Rekvig, O. (2008) Lupus nephritis: the central role of nucleosomes revealed. American Journal of Pathology, 172, 275-283.

[26]   Patole, P., Pawar, R., Lech, M., et al. (2006) Expression and regulation of Toll-like receptors in lupus-like immune complex glomerulonephritis of MRL-Fas(lpr) mice. Nephrol Dial Transplant, 21, 3062-3073. doi:10.1093/ndt/gfl336

[27]   Means, T., Latz, E., Hayashi, F., et al. (2005) Human lupus autoantibody-DNA complexes activate DCs through cooperation of CD32 and TLR9. Journal of Clinical Investigation, 115, 407-417.