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This Article Full Text Full Text (PDF) All Versions of this Article: ASN.2004110917v1 16/11/3281    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yung, S. Articles by Chan, T. M. Search for Related Content PubMed PubMed Citation Articles by Yung, S. Articles by Chan, T. M.

Effect of Human Anti-DNA Antibodies on Proximal Renal Tubular Epithelial Cell Cytokine Expression: Implications on Tubulointerstitial Inflammation in Lupus Nephritis

Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong

Address correspondence to: Prof. Tak Mao Chan or Dr. Susan Yang, Department of Medicine, University of Hong Kong, Room 303 New Clinical Building, Queen Mary Hospital, Pokfulam Road, Hong Kong. Phone: 852-2855-4041; Fax: 852-2872-5828; dtmchan{at}hkucc.hku.hk

Received for publication November 17, 2004. Accepted for publication August 9, 2005.

This study aimed to investigate the effects of human anti-DNA antibodies (Ab) from patients with lupus on renal proximal tubular epithelial cells (PTEC), focusing on alterations in cell morphology and proinflammatory cytokine synthesis. Immunohistochemistry showed increased tubulointerstitial IL-6 expression and IgG deposition in renal biopsies from patients with diffuse proliferative lupus nephritis, not observed in controls or membranous lupus nephritis, which correlated with the severity of inflammatory cell infiltration. Sera from patients with lupus nephritis contained IgG that bound to cultured PTEC. Such binding increased with disease activity and correlated with the level of anti-DNA Ab. Incubation of PTEC with anti-DNA Ab that were isolated during active (active Ab) or inactive (inactive Ab) disease induced IL-6 synthesis, both apically and from the basolateral aspect. This was accompanied by altered cell morphology, increased cell proliferation (P < 0.05), and lactate dehydrogenase release (P < 0.05). The binding of inactive Ab and active Ab to PTEC resulted in differential and sequential upregulation of TNF-, IL-1, and IL-6 secretion (P < 0.05). Early induction of TNF- was observed with active Ab; the two then acted synergistically to induce IL-6 secretion. Exposure of PTEC to inactive Ab was associated with modest induction of TNF-, which was not involved in downstream induction of other proinflammatory peptides. These data suggest distinct immunopathogenetic mechanisms during disease flare or remission. Conditioned media from human mesangial cells acted synergistically with anti-DNA Ab to induce cytokine secretion in PTEC. Results from these studies underscore the pivotal role of PTEC in the pathogenesis of tubulointerstitial inflammation and fibrosis in lupus nephritis.

This article has been cited by other articles:

				T. Chan Mycophenolate mofetil in the treatment of lupus nephritis - 7 years on Lupus, July 1, 2008; 17(7): 617 - 621. [PDF]

				S. Lui, S Yung, R Tsang, F Zhang, K. Chan, S Tam, and T. Chan Rapamycin prevents the development of nephritis in lupus-prone NZB/W F1 mice Lupus, April 1, 2008; 17(4): 305 - 313. [Abstract] [PDF]

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673