caa a22 4500 445885319 CHVBK 20180317145557.0 cr unu---uuuuu 170323e20111201xx s 000 0 eng 10.1007/s00011-011-0370-1 doi (NATIONALLICENCE)springer-10.1007/s00011-011-0370-1 TLR4 but not TLR2 regulates inflammation and tissue damage in acute pancreatitis induced by retrograde infusion of taurocholate [Elektronische Daten] [Darbaz Awla, Aree Abdulla, Sara Regnér, Henrik Thorlacius] 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. Experimental design: AP was induced by retrograde infusion of sodium taurocholate into the pancreatic duct in wild-type, TLR2- and TLR4-deficient mice. Samples were collected 24h 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. Conclusion: Our data suggest a role for TLR4 but not TLR2 in the pathogenesis of severe AP in mice. Springer Basel AG, 2011 Toll-like receptors nationallicence Amylase nationallicence Chemokines nationallicence Inflammation nationallicence Neutrophils nationallicence Pancreatitis nationallicence AP : Acute pancreatitis nationallicence MPO : Myeloperoxidase nationallicence MNL : Monomorphonuclear leukocytes nationallicence PBS : Phosphate-buffered saline nationallicence PMNL : Polymorphonuclear leukocytes nationallicence RIA : Radioimmunoassay nationallicence TAP : Trypsinogen activation peptide nationallicence TLR : Toll-like receptor nationallicence HPF : High-power field nationallicence Awla Darbaz Department of Clinical Sciences, Section for Surgery Malmö, Lund University, 205 02, Malmö, Sweden aut Abdulla Aree Department of Clinical Sciences, Section for Surgery Malmö, Lund University, 205 02, Malmö, Sweden aut Regnér Sara Department of Clinical Sciences, Section for Surgery Malmö, Lund University, 205 02, Malmö, Sweden aut Thorlacius Henrik Department of Clinical Sciences, Section for Surgery Malmö, Lund University, 205 02, Malmö, Sweden aut Inflammation Research SP Birkhäuser Verlag Basel 60/12(2011-12-01), 1093-1098 1023-3830 60:12<1093 2011 60 11 https://doi.org/10.1007/s00011-011-0370-1 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00011-011-0370-1 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Awla Darbaz Department of Clinical Sciences, Section for Surgery Malmö, Lund University, 205 02, Malmö, Sweden aut NATIONALLICENCE 700 1- Abdulla Aree Department of Clinical Sciences, Section for Surgery Malmö, Lund University, 205 02, Malmö, Sweden aut NATIONALLICENCE 700 1- Regnér Sara Department of Clinical Sciences, Section for Surgery Malmö, Lund University, 205 02, Malmö, Sweden aut NATIONALLICENCE 700 1- Thorlacius Henrik Department of Clinical Sciences, Section for Surgery Malmö, Lund University, 205 02, Malmö, Sweden aut NATIONALLICENCE 773 0- Inflammation Research SP Birkhäuser Verlag Basel 60/12(2011-12-01), 1093-1098 1023-3830 60:12<1093 2011 60 11 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer