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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Transl+Med
2015 ; 13
(ä): 178
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Anti-dsDNA antibodies induce inflammation via endoplasmic reticulum stress in
human mesangial cells
#MMPMID26040555
Zhang H
; Zhao C
; Wang S
; Huang Y
; Wang H
; Zhao J
; Yang N
J Transl Med
2015[Jun]; 13
(ä): 178
PMID26040555
show ga
BACKGROUND: Anti-dsDNA antibodies play an important role in the pathogenesis of
lupus nephritis (LN). Endoplasmic reticulum (ER) stress is a physical reaction
under stressful condition and can cause inflammation when stimulation is
sustained. This study investigated the roles of ER stress in anti-dsDNA
antibody-induced inflammation response in human mesangial cells (HMCs). METHOD:
Anti-dsDNA antibodies isolated from LN patients were used to stimulate HMCs. The
expression of GRP78, PERK, p-PERK, p-eIF2?, ATF4, p-IRE1?, ATF6 and CHOP in HMCs
was measured by western blot. NF-?B activation was detected by examining nuclear
translocation of NF-?B p65. The expression and production of IL-1?, TNF-? and
MCP-1 were examined by qPCR and ELISA. RESULTS: Flow cytometry and cellular ELISA
showed that anti-dsDNA antibodies can bind to HMCs. The binding was not inhibited
by blockage of Fc receptor. Anti-dsDNA antibody stimulation significantly
enhanced the expression of GRP78, p-PERK, p-eIF2? and ATF4 in HMCs. However, no
significant increase in the expression of p-IRE1? and ATF6 was found. In
addition, anti-dsDNA antibodies also significantly increased the activation of
NF-?B and upregulated the expression of IL-1?, TNF-? and MCP-1, which were
suppressed by pretreatment of HMCs with chemical ER stress inhibitor 4-PBA.
Transfection of specific ATF4 siRNA also significantly reduced the activation of
NF-?B and expression of proinflammatory cytokines. CONCLUSION: Anti-dsDNA
antibodies induce NF-?B activation and inflammation in HMCs via PERK-eIF2?-ATF4
ER stress pathway.