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Activation, Inflammatory cytokines, chemokines, cytoprotective gene pathways leads to Activation, Dendritic Cells
Key Event Relationship Overview
AOPs Referencing Relationship
|AOP Name||Adjacency||Weight of Evidence||Quantitative Understanding||Point of Contact||Author Status||OECD Status|
|Covalent Binding of Low Molecular Weight Organic Chemicals to Proteins leads to Sensitisation (Sensitization) of the Respiratory Tract||adjacent||Low||Not Specified||Kristie Sullivan (send email)||Under Development: Contributions and Comments Welcome||Under Development|
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 immune responses in dendritic cells associated with respiratory sensitization.
Evidence Supporting this KER
(Silva et al., 2014) found that Hexamethylene diisocyanate 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).
Uncertainties and Inconsistencies
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.