API

Relationship: 236

Title

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Peptide Oxidation leads to Increased, Activation and Recruitment of Hepatic macrophages (Kupffer Cells)

Upstream event

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Peptide Oxidation

Downstream event

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Increased, Activation and Recruitment of Hepatic macrophages (Kupffer Cells)

Key Event Relationship Overview

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AOPs Referencing Relationship

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Taxonomic Applicability

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Sex Applicability

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Life Stage Applicability

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How Does This Key Event Relationship Work

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Phagocytosis of necrotic debris, iron uptake, stimulation by ROS and/or diffusible aldehydes, also deriving from parenchymal and sinusoidal endothelial cells, are among the initial triggers of Kupffer cells. Certainly involved is the NADPH oxidase at the plasma membrane level, strongly up-regulated by the increased phagocytic activity, but also the inducible NO synthase, with consequent harmful reaction between ROS and NO. While lipid peroxidation-derived aldehydes certainly are not the only molecules involved in the activation of Kupffer cell following liver injury of different aetiology, they may provide a significant contribution. Experiments on cells of the macrophage lineage showed significant aldehyde-induced stimulation of the activity of protein kinase C, an enzyme involved in several signal transduction pathway. Further, HNE was demonstrated to up-regulate TGFb1 expression and synthesis in isolated rat Kupffer cells.

Weight of Evidence

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Empirical Support for Linkage

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Uncertainties or Inconsistencies

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Quantitative Understanding of the Linkage

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Evidence Supporting Taxonomic Applicability

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References

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Poli, Molecular Aspects of Medicine 21 (2000) 49±98