Impaired TGF-beta signalling enhances peritoneal inflammation induced by E. coli in rats.
BACKGROUND
Peritonitis is a common and severe complication of peritoneal dialysis (PD). Although TGF-beta is a key mediator in peritoneal fibrosis with chronic PD, its role in acute peritoneal inflammation remains unclear.


METHODS
Potential role of TGF-beta signalling in acute peritonitis was investigated in a rat model by infecting peritoneum with E. coli and in primary culture of peritoneal mesothelial cells (PMC) by LPS.


RESULTS
We found that a single infection of E. coli caused an acute, but transient peritonitis by a significant increase in ascites white blood cells (WBC), peritoneal CD45+ leukocytes, upregulation of TNFalpha, activation of NF-kappaB/p65 and impaired peritoneal function (all P < 0.01). Interestingly, spontaneous recovery of acute peritonitis occurred with upregulation of TGF-beta1 and activation of Smad2/3, suggesting a protective role of TGF-beta signalling in acute peritonitis. This was demonstrated by the finding that blockade of the TGF-beta signalling pathway with gene transfer of Smad7 inactivated peritoneal Smad2/3 but worsened E. coli-induced, NF-kappaB-dependent peritoneal inflammation and peritoneal dysfunction (all P < 0.01). Furthermore, studies in vitro also found that impaired TGF-beta signalling by overexpressing Smad7 in PMC were able to overcome the inhibitory effect of TGF-beta on LPS-induced, NF-kappaB-mediated peritoneal inflammation.


CONCLUSIONS
Results from this study demonstrate that TGF-beta signalling is essential in protection against acute peritoneal inflammation induced by bacterial infection.
Wang
Xin
X
Department of Nephrology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
Nie
Jing
J
Jia
Zhanjun
Z
Feng
Mingliang
M
Zheng
Zhihua
Z
Chen
Wenfang
W
Li
Xiaoyan
X
Peng
Wenxing
W
Zhang
Shehong
S
Sun
Liao
L
Mao
Haiping
H
Lan
Hui Yao
HY
Yu
Xueqing
X
D000818:Animals; D004927:Escherichia coli Infections / Q000276:immunology*; D008297:Male; D010538:Peritonitis / Q000276:immunology* / Q000382:microbiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D051906:Smad7 Protein / Q000096:biosynthesis; D016212:Transforming Growth Factor beta / Q000502:physiology*
D051906:Smad7 Protein; C497808:Smad7 protein, rat; D016212:Transforming Growth Factor beta