title: TLR4 but not TLR2 regulates inflammation and tissue damage in acute pancreatitis induced by retrograde infusion of taurocholate.
abstract: OBJECTIVE
  Neutrophil infiltration is a key regulator in the pathophysiology of acute pancreatitis (AP), although the impact of Toll-like receptors (TLRs) in AP remains elusive. The aim of this study was to define the role of TLR2 and TLR4 in leukocyte recruitment and tissue damage in severe AP.
  
  
  METHODS
  AP was induced by retrograde infusion of sodium taurocholate into the pancreatic duct in wild-type, TLR2- and TLR4-deficient mice. Samples were collected 24 h after induction of AP.
  
  
  RESULTS
  Taurocholate challenge caused a clear-cut pancreatic damage characterized by increased acinar cell necrosis, neutrophil infiltration, focal hemorrhage and edema formation, as well as increased levels of blood amylase and CXCL2 (macrophage inflammatory protein-2) in the pancreas and serum. Moreover, challenge with taurocholate increased activation of trypsinogen in the pancreas. Notably, TLR2 gene-deficient mice exhibited a similar phenotype to wild-type mice after challenge with taurocholate. In contrast, tissue damage, pancreatic and lung myeloperoxidase (MPO) activity, serum and pancreatic levels of CXCL2 as well as blood amylase were significantly reduced in TLR4-deficient mice exposed to taurocholate. However, taurocholate-induced activation of trypsinogen was intact in TLR4-deficient mice.
  
  
  CONCLUSIONS
  Our data suggest a role for TLR4 but not TLR2 in the pathogenesis of severe AP in mice.
authors.affiliation: Department of Clinical Sciences, Section for Surgery Malmö, Lund University, 205 02 Malmö, Sweden.
authors.forename: Darbaz
authors.initials: D
authors.lastname: Awla
authors.forename: Aree
authors.initials: A
authors.lastname: Abdulla
authors.forename: Sara
authors.initials: S
authors.lastname: Regnér
authors.forename: Henrik
authors.initials: H
authors.lastname: Thorlacius
mesh_terms: D000818:Animals; D054426:Chemokine CXCL2 / Q000097:blood / Q000378:metabolism; D007958:Leukocyte Count; D008168:Lung / Q000201:enzymology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020556:Neutrophil Infiltration; D019283:Pancreatitis, Acute Necrotizing / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism; D013656:Taurocholic Acid / Q000009:adverse effects; D051195:Toll-Like Receptor 2 / Q000172:deficiency / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014362:Trypsinogen / Q000378:metabolism
chemical_list: D054426:Chemokine CXCL2; C404915:Cxcl2 protein, mouse; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D013656:Taurocholic Acid; D014362:Trypsinogen; D009195:Peroxidase