API

Relationship: 1699

Title

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Activation, Inflammatory cytokines, chemokines, cytoprotective gene pathways leads to Activation, Dendritic Cells

Upstream event

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Activation, Inflammatory cytokines, chemokines, cytoprotective gene pathways

Downstream event

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Activation, Dendritic Cells

Key Event Relationship Overview

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AOPs Referencing Relationship

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Taxonomic Applicability

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Term Scientific Term Evidence Link
human Homo sapiens High NCBI

Sex Applicability

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Sex Evidence
Unspecific

Life Stage Applicability

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Term Evidence
All life stages

Key Event Relationship Description

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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

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Biological Plausibility

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(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).

Empirical Evidence

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(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

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Quantitative Understanding of the Linkage

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Response-response Relationship

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Time-scale

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Known modulating factors

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Known Feedforward/Feedback loops influencing this KER

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Domain of Applicability

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References

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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.