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Up-regulated renal expression of TNF- signalling adapter proteins in lupus glomerulonephritis

Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China

X Yang

Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China

Y Ji

Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China

W Chen

Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China

W Guan

Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China

SF Zhou

Division of Chinese Medicine, School of Health Sciences, WHO Collaborating Center for Traditional Medicine, RMIT University, Victoria, Australia

X Yu

Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China

The role of tumour necrosis factor (TNF-) signalling adapters in lupus nephritis (LN) is poorly understood. This study investigated renal expression of TNF- and TNF signalling adapter proteins, including TNF receptor-associated death domain protein (TRADD), receptor-interacting protein (RIP) and TNF receptor-associated factor-2 (TRAF-2) in patients with LN. The renal expression of proliferating cell nuclear antigen (PCNA) and CD68 was also measured. The study showed that glomerular and tubular expression of TNF-, TRADD, RIP and TRAF-2 was significantly up-regulated in class III and IV LN in which the intense staining was observed on the crescents, proximal and distal tubules and interstitial mononuclear cells. The number of PCNA-positive cells and CD68-positive cells (macrophages) was increased obviously in class III and IV LN. There was a correlation between the expression levels of TNF-, TRADD, RIP, TRAF-2 and the number of PCNA-positive or CD68-positive cells and active index of renal pathology. These findings suggest that TNF- and TNF- adapters in patients with LN play a role in immunopathogenic injury via transmitting abnormal cell proliferating and proinflammatory signals. The findings have provided further insights into the role of TNF- and its adapter proteins in the pathogenesis of LN and have important therapeutic implications.

Key Words: adapter protein • immunohistologic analysis • lupus nephritis • signal transduction • TNF-

Lupus, Vol. 18, No. 2, 116-127 (2009)
DOI: 10.1177/0961203308094764


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