Z Gastroenterol 2014; 52 - P_5_06
DOI: 10.1055/s-0033-1361015

Deletion of Formyl-peptide receptors lead to an increased inflammatory response and enhanced liver injury following a bacterial induced hepatitis

A Giebeler 1, U Neumann 1, LO Brandenburg 2
  • 1University Hospital RWTH Aachen, Departement of Surgery, Aachen, Germany
  • 2University Hospital RWTH Aachen, Institute for Anatomy and Cell Biology, Aachen, Germany

Introduction: The Formyl-peptide-receptor 1 and the formyl-peptide-receptor 2 (FPR1 and FPR2) were identified as receptors with a different affinity for the pathogen-associated-molecular-pattern (PAMP) N-formylmethionyl-leucyl-phenylalanine (fMLF). The tripeptide fMLF is a component of the bacterial membrane. During apoptosis it is secreted by the mitochondria of eukaryotic cells. Furthermore FPR1 and 2 are described as highly relevant factors for the chemotaxis of monocytes and neutrophils. So far their role during the acute liver injury has not been investigated.

Material and Methods: Constitutive knockout mice for FPR1 (mFPR1-/-), FPR2 (mFPR2-/-) and wild type (WT) mice were challenged with 100 µg LPS i.p. for 6 hours. Afterwards the liver and blood were sampled for further analysis.

Results: The analysis of transaminases showed a significant increase of ALT and AST 6h after LPS stimulus in mFPR deficient mice in comparison to WT mice. These elevated levels of transaminases were in concordance with significantly higher expression of pro-inflammatory genes such as IL-6, TNF-α and CXCL1 in mice lacking mFPR1 or 2. As a result of the higher inflammatory gene expression, a higher number of cells positive for CD11b and Ly6G were present in the livers of the mFPR1- and the mFPR2-knockout mice The higher pro-inflammatory gene expression matched with the significant higher presence of CD11b+ and Ly6G+ cells in the livers of mFPR1-/- and mFPR2-/- mice

Additionally to the prior findings mFPR1 and mFPR2 deficient mice seem to be more susceptible to apoptosis by showing a significant higher number of TUNEL+ cells in the liver compared to wild type mice

Conclusion: These results suggest a prominent role of FPRs in the regulation of the hepatic inflammatory response following a bacterial induced liver damage. Either the deletion of mFPR1 or mFPR2 leads to a deregulation of the inflammatory response compared to wild type mice, associated with a higher liver injury represented by higher transaminases and apoptotic cells. However the role of FPRs during the inflammatory liver diseases remains to be investigated in more detail.