TLR4 but not TLR2 regulates inflammation and tissue damage in acute pancreatitis induced by retrograde infusion of taurocholate

Darbaz Awla, Aree Abdulla, Sara Regnér, Henrik Thorlacius
Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.] 2011, 60 (12): 1093-8

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 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.

CONCLUSION: Our data suggest a role for TLR4 but not TLR2 in the pathogenesis of severe AP in mice.


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