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

Abstract

The role of tumour necrosis factor (TNF-alpha) signalling adapters in lupus nephritis (LN) is poorly understood. This study investigated renal expression of TNF-alpha 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-alpha, 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-alpha, 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-alpha and TNF-alpha 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-alpha and its adapter proteins in the pathogenesis of LN and have important therapeutic implications.

• Authors: L Zhu, X Yang, Y Ji, W Chen, W Guan, S F Zhou, X Yu
• Journal: Lupus (Lupus) Vol. 18 Issue 2 Pg. 116-27 (Feb 2009) ISSN: 0961-2033 [Print] England
• PMID: 19151112 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD
• Antigens, Differentiation, Myelomonocytic
• CD68 antigen, human
• Proliferating Cell Nuclear Antigen
• TNF Receptor-Associated Death Domain Protein
• TNF Receptor-Associated Factor 2
• Tumor Necrosis Factor-alpha
• Receptor-Interacting Protein Serine-Threonine Kinases

Topics

• Adult
• Antigens, CD (metabolism)
• Antigens, Differentiation, Myelomonocytic (metabolism)
• Case-Control Studies
• Female
• Humans
• Kidney Glomerulus (metabolism)
• Kidney Tubules (metabolism)
• Lupus Nephritis (metabolism)
• Male
• Middle Aged
• Proliferating Cell Nuclear Antigen (metabolism)
• Receptor-Interacting Protein Serine-Threonine Kinases (metabolism)
• Signal Transduction
• TNF Receptor-Associated Death Domain Protein (metabolism)
• TNF Receptor-Associated Factor 2 (metabolism)
• Tumor Necrosis Factor-alpha (metabolism)
• Up-Regulation
• Young Adult