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Event: 1172
Key Event Title
Increase activation, Nuclear factor kappa B (NF-kB)
Short name
Biological Context
Level of Biological Organization |
---|
Cellular |
Cell term
Cell term |
---|
epithelial cell |
Organ term
Organ term |
---|
tissue |
Key Event Components
Process | Object | Action |
---|---|---|
regulation of I-kappaB kinase/NF-kappaB signaling | increased |
Key Event Overview
AOPs Including This Key Event
AOP Name | Role of event in AOP | Point of Contact | Author Status | OECD Status |
---|---|---|---|---|
AT1R, lung fibrosis | KeyEvent | Young Jun Kim (send email) | Under development: Not open for comment. Do not cite | Under Development |
TLR9 activation leading to Multi Organ Failure and ARDS | KeyEvent | Gillina Bezemer (send email) | Under development: Not open for comment. Do not cite | |
Binding to ACE2 leads to lung fibrosis | KeyEvent | Young Jun Kim (send email) | Open for comment. Do not cite | Under Development |
DNA damage and metastatic breast cancer | KeyEvent | Usha Adiga (send email) | Under development: Not open for comment. Do not cite | Under Development |
Taxonomic Applicability
Term | Scientific Term | Evidence | Link |
---|---|---|---|
Homo sapiens | Homo sapiens | High | NCBI |
Life Stages
Life stage | Evidence |
---|---|
Not Otherwise Specified | Moderate |
Sex Applicability
Term | Evidence |
---|---|
Mixed |
Key Event Description
The NF-kB pathway consists of a series of events where the transcription factors of the NF-kB family play a key role. The proinflammatory cytokine (IL-1beta) can be activated by NF-kB , including Reactive Oxygen Species produced by NADPH oxidase (NOX). Upon pathway activation, the IKK complex will be phosphorylated, which in turn phosphorylates IkBa. There, this transcription factor can express pro-inflammatory and pro-fibrotic genes. This can be achieved by ROS, IKK enhancer or nuclear translocation enhancer.
How It Is Measured or Detected
NF-kB transcriptional activity: Beta lactamase reporter gene assay (Miller et al. 2010). NF-kB transcription: Lentiviral NF-kB GFP reporter with flow cytometry (Moujalled et al. 2012)
NF-κB translocation: RelA-GFP reporter assay (Frederiksson 2012) (Huppelschoten 2017)
IκBa phosphorylation: Western blotting (Miller et al. 2010)
NF-κB p65 (Total/Phospho) ELISA
ELISA for IL-6, IL-8, and Cox
Domain of Applicability
The ROS directly influences NF-κB signalling, resulting in differential production of cytokines and chemokines (McKay and Cidlowski, 1999; Pernis, 2007). NF-κB regulates pro-inflammatory responses that are transcriptionally mediated by NF‑κB.