Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 269.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 269.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 269.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 269.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 269.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\27881147
.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Arthritis+Res+Ther
2016 ; 18
(1
): 271
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
p53 predominantly regulates IL-6 production and suppresses synovial inflammation
in fibroblast-like synoviocytes and adjuvant-induced arthritis
#MMPMID27881147
Zhang T
; Li H
; Shi J
; Li S
; Li M
; Zhang L
; Zheng L
; Zheng D
; Tang F
; Zhang X
; Zhang F
; You X
Arthritis Res Ther
2016[Nov]; 18
(1
): 271
PMID27881147
show ga
BACKGROUND: Dominant-negative somatic mutations of p53 has been identified in the
synovium of patients with rheumatoid arthritis (RA), in which interleukin (IL)-6
has been established as a pivotal inflammatory cytokine. The aim of this study
was to clarify the significance of p53 in the longstanding inflammation in RA by
modulating IL-6. METHODS: We established adjuvant-induced arthritis (AIA) in
Lewis rats and treated them with p53 activator, and then analyzed the
histopathology of the synovium and IL-6 expression. Human fibroblast-like
synoviocytes (FLS) were cultured and transfected with p53-siRNA or transduced
with adenovirus (Ad)-p53, and then assessed with MTT, TUNEL staining, and
luciferase assay. IL-1?, tumor necrosis factor (TNF)-? and IL-17 were used to
stimulate FLS, and subsequent IL-6 expression as well as relevant signal pathways
were explored. RESULTS: p53 significantly reduced synovitis as well as the IL-6
level in the AIA rats. It controlled cell cycle arrest and proliferation, but not
apoptosis. Proinflammatory cytokines inhibited p53 expression in FLS, while p53
significantly suppressed the production of IL-6. Furthermore, IL-6 expression in
p53-deficient FLS was profoundly reduced by NF-kappaB, p38, JNK, and ERK
inhibitors. CONCLUSION: Our findings reveal a novel function of p53 in
controlling inflammatory responses and suggest that p53 abnormalities in RA could
sustain and accelerate synovial inflammation mainly through IL-6. p53 may be a
key modulator of IL-6 in the synovium and plays a pivotal role in suppressing
inflammation by interaction with the signal pathways in RA-FLS. Interfering with
the p53 pathway could therefore be an effective strategy to treat RA.
free
free
free
