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Relationship: 2651
Title
Increased proinflammatory mediators leads to Activation, Dendritic Cells
Upstream event
Downstream event
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 | Arthur Author (send email) | Under Development: Contributions and Comments Welcome | Under Development |
Taxonomic Applicability
Sex Applicability
Life Stage Applicability
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.
Evidence Collection Strategy
Evidence Supporting this KER
Biological Plausibility
DCs express receptors for, and respond to, constitutive and inflammatory chemokines and other chemoattractants, such as platelet-activating factor and formyl peptides. Much investigation has gone into assessing the specific mechanistic events involved in skin sensitizer-caused DC migration. Ex vivo studies with intact human skin, epidermal sheets, and MUTZ-3-derived Langerhans cells (LC) show that fibroblasts mediate migration of cytokine-matured LC via chemokines, including CXCL12, CXCR4, and dermis-derived CCL2 and CCL5. (Ouwehand, et al., 2011) The relevance of these studies for respiratory sensitization is not known.
Empirical Evidence
(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). (Silva et al., 2014) also found that coincubation with the antioxidant N-acetyl cysteine and SOD decreased ERK phosphorylation in hexamethylene diisocyanate-treated THP-1 cells.