Lack of hepatic c-Met and gp130 expression is associated with an impaired antibacterial response and higher lethality after bile duct ligation

Giebeler, A.; Brandenburg, Lars‐Ove; Kaldenbach, M.; Erschfeld, S.; Wasmuth, Hermann E.; Wruck, Christoph Jan; Streetz, Konrad L.

doi:10.1038/labinvest.2012.122

Cited by 10 publications

(8 citation statements)

References 33 publications

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“…Earlier findings indicate a relevant role of mFPRs in the clearance of the sepsis [14]. A previous publication of our group linked functional signalling cascades to a pro-survival phenotype in a murine model of acute biliary injury [22]. The analysis of liver inflammation in the cholestatic liver injury model for the variation of mFPR expression at the time point 24 h and 72 h post BDL suggests that a coordinated presence and expression is important for maintaining the equilibrium of inflammation also to avoid a chronic inflammation which leads to liver fibrosis.…”

Section: Discussionmentioning

confidence: 83%

“…The role of bacterial translocation in liver diseases has changed in the last years. Being suggested as a late stage event [20], it was shown that early bacterial translocation is a main reason for the establishment of liver fibrosis [21] and the progress of liver injury and survival of the bacterial infection was furthermore linked to the bacterial burden [22].…”

Section: Introductionmentioning

confidence: 99%

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Deficiency of Formyl Peptide Receptor 1 and 2 Is Associated with Increased Inflammation and Enhanced Liver Injury after LPS-Stimulation

et al. 2014

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IntroductionFormyl peptide-receptor 1 and 2 (FPR1 and FPR2) in mice were identified as receptors with contrary affinity for the PAMP fMLF. Formyl-methionyl-leucyl-phenylalanine is either part of the bacterial membrane and is secreted by the mitochondria of eukaryotic ceslls during apoptosis. Furthermore FPR1 and 2 are described as highly relevant factors for the chemotaxis of immune cells. Their role during the acute liver injury has not been investigated yet.Materials and MethodsConstitutive knockout mice for FPR1 (mFPR1-/-), FPR2 (mFPR2-/-) and wild type (WT) mice were challenged with LPS i.p. for 3 h and 6 h. Liver and serum were sampled for further analysis.ResultsLiver transaminases were elevated in all mice 3 h and 6 h post LPS stimulation. Gene expression analysis displayed a reduced expression of the pro-inflammatory cytokines IL-6 and CXCL1 after 3 h in the mFPR1-/- compared to wild type and mFPR2-/- mice. After 6 h, IL-6, TNF-α and CXCL1 were significantly higher in mice lacking mFPR1 or 2. Consistent to these findings the numbers of CD11b+ and Ly6G+ immune cells were altered in the livers. The analysis of TLR2 and TLR4 revealed time and genotype specific changes in theirs gene expression. Additionally, the liver in mFPR1- and mFPR2-deficient mice seem to be more susceptible to apoptosis by showing a significant higher number of TUNEL+-cells in the liver than WT-mice and displayed less Ki67-positive nuclei in the liver.ConclusionThe results suggest a prominent role of FPRs in the regulation of the hepatic inflammatory response after LPS induced liver injury. Deletion of mFPR1 or mFPR2 leads to deregulation of the inflammatory response compared to WT mice, associated with more severe liver injury represented by higher levels of transaminases, apoptotic cells and a reduced regenerative capacity.

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Section: Discussionmentioning

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Deficiency of Formyl Peptide Receptor 1 and 2 Is Associated with Increased Inflammation and Enhanced Liver Injury after LPS-Stimulation

et al. 2014

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“…Many studies have indicated that activated NF-κB(p65) up-regulated the secretion of large amounts of inflammatory cytokines, such as TNF-α, and IL-6 during the initial phase of warm IRI121314. The interaction of cytokines leads to the non-functioning epithelium by increasing neutrophil adherence, causing disturbance of the biliary tract microcirculation, and inducing bile duct cell apoptosis111516. Consequently, activation of NF-κB(p65) has been considered to be a critical event in the initiation and perpetuation of bile duct warm IRI.…”

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confidence: 99%

Impact of Recombinant Globular Adiponectin on Early Warm Ischemia-Reperfusion Injury in Rat Bile Duct after Liver Transplantation

Yang

Gong

2014

Sci Rep

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Adiponectin (APN) is an adipocyte protein with anti-diabetic properties, which has been recently revealed to have anti-inflammatory activity in organ ischemia- reperfusion injury (IRI). However, little is known about its function in bile duct IRI after liver transplantation. Therefore, we investigated whether APN affects early warm IRI in rat bile duct using a liver autologous transplantation model. In our study, rats were randomly divided into three experimental groups: a sham group, a IRI group, and a APN group. The serum enzyme levels and BDISS scores of bile duct histology associated with bile duct injury, decreased after administration of APN. Subsequently, the expression of proinflammatory cytokines, such as tumor necrosis factor(TNF-α),.interleukin-6(IL-6) and myeloperoxidase (MPO) decreased. Furthermore, pretreatment with APN suppressed the activation of nuclear factor-kappa B (NF-κB) (p65), a transcription factor involved in inflammatory reactions, compared to other two groups. Administration of APN also downregulated the expression of Fas protein and attenuated caspase-3 activity to decrease bile duct apoptosis. Our results illustrate that APN protects the rat bile duct against early warm IRI by suppressing the inflammatory response and hepatocyte apoptosis, and NF-κB (p65) plays an important role in this process.

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“…Other tissues with epithelial layers (lung, 39 pancreas, 40 among others) experience elevated HGF during a variety of pathological conditions. Giebeler et al 41 demonstrated that HGF and inflammatory cytokines (IL-6, TNF-a) are upregulated during cholestatic liver injury. In addition, this group provided evidence that c-met-dependent signaling leads to TLR4dependent pathway activation.…”

Section: Discussionmentioning

confidence: 99%

HGF Signaling Impacts Severity ofPseudomonas aeruginosaKeratitis

Jiang¹,

McClellan²,

Barrett³

et al. 2014

Invest. Ophthalmol. Vis. Sci.

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Lack of hepatic c-Met and gp130 expression is associated with an impaired antibacterial response and higher lethality after bile duct ligation

Cited by 10 publications

References 33 publications

Deficiency of Formyl Peptide Receptor 1 and 2 Is Associated with Increased Inflammation and Enhanced Liver Injury after LPS-Stimulation

Deficiency of Formyl Peptide Receptor 1 and 2 Is Associated with Increased Inflammation and Enhanced Liver Injury after LPS-Stimulation

Impact of Recombinant Globular Adiponectin on Early Warm Ischemia-Reperfusion Injury in Rat Bile Duct after Liver Transplantation

HGF Signaling Impacts Severity ofPseudomonas aeruginosaKeratitis

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