Relationship: 236
Title
Upstream event
Peptide OxidationDownstream event
Increased, Activation and Recruitment of Hepatic macrophages (Kupffer Cells)
Key Event Relationship Overview
AOPs Referencing Relationship
Taxonomic Applicability
Sex Applicability
Life Stage Applicability
How Does This Key Event Relationship Work
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
Quantitative Understanding of the Linkage
Evidence Supporting Taxonomic Applicability
References
Poli, Molecular Aspects of Medicine 21 (2000) 49±98