Upstream eventActivation, Inflammatory cytokines, chemokines, cytoprotective gene pathways
Activation, Dendritic Cells
Key Event Relationship Overview
AOPs Referencing Relationship
|AOP Name||Adjacency||Weight of Evidence||Quantitative Understanding|
|Sensitisation of the Respiratory Tract induced by Covalent Binding of Low Molecular Weight Organic Chemicals to Proteins||adjacent|
Life Stage Applicability
|All life stages|
Key Event Relationship Description
The presence of cellular danger signals at the local exposure site leads to the induction and amplification of lung immune responses associated with respiratory sensitization.
Evidence Supporting this KER
(Silva et al., 2014) found that HDI increased ROS by inhibiting superoxide dismutase (SOD1) in THP-1 cells. Increased ROS also led to extracellular signal-related kinase (ERK) signaling pathway phosphorylation and the transcription of cytoprotective and maturation pathways (HMOX1 and CD83).
(Silva et al., 2014) found that coincubation with the antioxidant N-acetyl cysteine and SOD decreased ERK phosphorylation in HDI-treated THP-1 cells.
Uncertainties and Inconsistencies
Quantitative Understanding of the Linkage
Known modulating factors
Known Feedforward/Feedback loops influencing this KER
Domain of Applicability
SILVA, A., NUNES, C., MARTINS, J., DINIS, T. C., LOPES, C., NEVES, B. & CRUZ, T. 2014. Respiratory sensitizer hexamethylene diisocyanate inhibits SOD 1 and induces ERK-dependent detoxifying and maturation pathways in dendritic-like cells. Free Radic Biol Med, 72, 238-46.