title: Impaired TGF-beta signalling enhances peritoneal inflammation induced by E. coli in rats.
abstract: 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.
authors.affiliation: Department of Nephrology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Nie
authors.forename: Zhanjun
authors.initials: Z
authors.lastname: Jia
authors.forename: Mingliang
authors.initials: M
authors.lastname: Feng
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Zheng
authors.forename: Wenfang
authors.initials: W
authors.lastname: Chen
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Li
authors.forename: Wenxing
authors.initials: W
authors.lastname: Peng
authors.forename: Shehong
authors.initials: S
authors.lastname: Zhang
authors.forename: Liao
authors.initials: L
authors.lastname: Sun
authors.forename: Haiping
authors.initials: H
authors.lastname: Mao
authors.forename: Hui Yao
authors.initials: HY
authors.lastname: Lan
authors.forename: Xueqing
authors.initials: X
authors.lastname: Yu
mesh_terms: 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*
chemical_list: D051906:Smad7 Protein; C497808:Smad7 protein, rat; D016212:Transforming Growth Factor beta