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. CONCLUSION: Results from this study demonstrate that TGF-beta signalling is essential in protection against acute peritoneal inflammation induced by bacterial infection.
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. CONCLUSION: Results from this study demonstrate that TGF-beta signalling is essential in protection against acute peritoneal inflammation induced by bacterial infection.
Authors: Jesús Loureiro; Abelardo Aguilera; Rafael Selgas; Pilar Sandoval; Patricia Albar-Vizcaíno; María Luisa Pérez-Lozano; Vicente Ruiz-Carpio; Pedro L Majano; Santiago Lamas; Fernando Rodríguez-Pascual; Francisco Borras-Cuesta; Javier Dotor; Manuel López-Cabrera Journal: J Am Soc Nephrol Date: 2011-07-08 Impact factor: 10.121
Authors: Elerson C Costalonga; Luiza J de Freitas; Deise da S P Aragone; Filipe M O Silva; Irene L Noronha Journal: PLoS One Date: 2017-09-05 Impact factor: 3.240
Authors: Alferso C Abrahams; Sayed M Habib; Amélie Dendooven; Bruce L Riser; Jan Willem van der Veer; Raechel J Toorop; Michiel G H Betjes; Marianne C Verhaar; Christopher J E Watson; Tri Q Nguyen; Walther H Boer Journal: PLoS One Date: 2014-11-10 Impact factor: 3.240