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Relationship: 1814
Title
Decreased IL-1 production leads to Impaired IL-1 signaling
Upstream event
Downstream event
Key Event Relationship Overview
AOPs Referencing Relationship
Taxonomic Applicability
Sex Applicability
Sex | Evidence |
---|---|
Unspecific | High |
Life Stage Applicability
Term | Evidence |
---|---|
All life stages | High |
Key Event Relationship Description
The initial step of IL-1 signaling is the bidning of IL-1 to IL-1 receptor. So, the decreased IL-1 production leads to decreased IL-1 signaling.
Evidence Supporting this KER
Biological Plausibility
The initial step in IL-1 signal transduction is a ligand-induced conformational change in the first extracellular domain of the IL-1RI that facilitates recruitment of IL-1RacP after binding of IL-1 to IL-1 receptor. Therefore, lack of IL-1 molecule cannot trigger IL-1 signaling.
Empirical Evidence
Uncertainties and Inconsistencies
Quantitative Understanding of the Linkage
Response-response Relationship
Time-scale
Known modulating factors
Known Feedforward/Feedback loops influencing this KER
Domain of Applicability
Although sex differences in immune responses are well known (Klein and Flanagan, 2016), there is no reports regarding the sex difference in IL-1 production, IL-1 function or susceptibility to infection as adverse effect of IL-1 blocking agent. Again, age-dependent difference in IL-1 signaling is not known.
The IL1B gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, and frog (https://www.ncbi.nlm.nih.gov/homologene/481), and the Myd88 gene is conserved in human, chimpanzee, Rhesus monkey, dog, cow, rat, chicken, zebrafish, mosquito, and frog (https://www.ncbi.nlm.nih.gov/homologene?Db=homologene&Cmd=Retrieve&list_uids=1849).
These data suggest that the proposed AOP regarding inhibition of IL-1 signaling is not dependent on life stage, sex, age or species.
References
Klein, S.L., Flanagan, K.L., 2016. Sex differences in immune responses. Nat Rev Immunol 16, 626-638.