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Relationship: 236
Title
Peptide Oxidation leads to Increased, Activation and Recruitment of Hepatic macrophages (Kupffer Cells)
Upstream event
Downstream event
Key Event Relationship Overview
AOPs Referencing Relationship
Taxonomic Applicability
Sex Applicability
Life Stage Applicability
Key Event Relationship Description
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.
Evidence Collection Strategy
Evidence Supporting this KER
Biological Plausibility
Empirical Evidence
Uncertainties and Inconsistencies
Known modulating factors
Quantitative Understanding of the Linkage
Response-response Relationship
Time-scale
Known Feedforward/Feedback loops influencing this KER
Domain of Applicability
References
Poli, Molecular Aspects of Medicine 21 (2000) 49±98