Up-regulated renal expression of TNF-alpha signalling adapter proteins in lupus glomerulonephritis.
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.
Zhu
L
L
Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
Yang
X
X
Ji
Y
Y
Chen
W
W
Guan
W
W
Zhou
S F
SF
Yu
X
X
D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007678:Kidney Glomerulus / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism*; D008181:Lupus Nephritis / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction; D053199:TNF Receptor-Associated Death Domain Protein / Q000378:metabolism; D047992:TNF Receptor-Associated Factor 2 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D015854:Up-Regulation; D055815:Young Adult; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D018809:Proliferating Cell Nuclear Antigen; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; D053199:TNF Receptor-Associated Death Domain Protein; D047992:TNF Receptor-Associated Factor 2; D014409:Tumor Necrosis Factor-alpha; C067980:CD68 antigen, human; D000097382:CD68 Molecule