Suppression of tumor necrosis factor receptor associated factor (TRAF)-2 attenuates the proinflammatory and proliferative effect of aggregated IgG on rat renal mesangial cells.
Immune-complex (IC) mediated glomerulonephritis (GN) is a common cause of chronic kidney disease associated with increased levels of tumor necrosis factor (TNF)-alpha in renal cells. TNF-alpha signaling pathways involve complicated interactions between multiple proteins including TNF-receptor-associated factor (TRAF)-2. We have previously found markedly up-regulated expression of TRAF-2 in renal tissues from IC mediated lupus nephritis patients. Here we investigated the effect of TRAF-2 on inflammatory response in rat mesangial cells (MCs). The results showed that treatment with soluble aggregated IgG (AIgG) resulted in a time- and dose-dependent increase in the expression of interleukin (IL)-1beta and IL-6. Significant cell proliferation was also observed after the treatment with soluble AIgG. Knockdown TRAF-2 by siRNA significantly suppressed soluble AIgG induced up-regulation of TRAF-2, IL-1beta, and IL-6. Meanwhile the cell proliferation was inhibited and apoptotic cells were increased. It was concluded that TRAF-2 could induce the proinflammatory and proliferative effects of soluble AIgG on rat MCs. Thus, TRAF-2 may represent a future target for therapy of IC mediated GN.
Zhu
Lang-Jing
LJ
Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
Yang
Xiao
X
Li
Xiao-Yan
XY
Liu
Qing-Hua
QH
Tang
Xue-Qing
XQ
Zhou
Shu-Feng
SF
Kong
Qing-Yu
QY
Axelsson
Jonas
J
Yu
Xue-Qing
XQ
D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D005921:Glomerulonephritis / Q000276:immunology*; D007105:Immune Complex Diseases / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology*; D007249:Inflammation / Q000276:immunology*; D053583:Interleukin-1beta / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D050527:Mesangial Cells / Q000166:cytology / Q000276:immunology*; D034622:RNA Interference; D051381:Rats; D047992:TNF Receptor-Associated Factor 2 / Q000235:genetics / Q000378:metabolism*
D000936:Antigen-Antibody Complex; D007074:Immunoglobulin G; D053583:Interleukin-1beta; D015850:Interleukin-6; D047992:TNF Receptor-Associated Factor 2