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UseCase19 cyclosporin

Dana Klassen edited this page Apr 20, 2011 · 3 revisions

Mechanism of Calcineurin inhibition by Cyclosporin A

Example of Immunosuppression through Calcineurin Inhibition

Context

Cyclosporin a is an immunosuppressant drug used to prevent host rejection in organ transplants.

Mechanism

Cyclosporine a binds to cyclophilin of immunocompetent lymphocytes. Complex formation results in inhibition of calcineurin which is responsible for activating transcription of interleukin 2. Calcineurin normally participates in dephosphorylation of transcription factor NF-AT which moves to the nucleus of the T-cell and increased the activity of genes encoding for interleukin-2. Cylcosporin a prevents dephosphorylation of NF-AT by binding to cyclophilin.

Knowledge base Challenges

Representational
   Biochemical

1. Restriction based on cell type

   Expression(language requirements)

Functional (Question and Answer)

Q. “Which mechanism involves cyclophilin?” A:“Mechanism of Calcineurin inhibition by Cyclosporin A” Query: Q. “Which chemical forms a complex with cyclophilin?” A: “Cyclosporin A binds to cyclophilin” Query: ‘chemical entity’ that ‘has disposition’ some (‘to be part of a complex’ and ‘in relation to’ some cyclophilin and ‘is realized in’ only ‘molecular complex formation’) Q. “Which chemical inhibits calcineurin?” A: “cyclosporin a” Query:

Process Models

‘cyclosporin a’ subClassof ‘chemical entity’ that (‘has disposition’ some (‘to be part of a complex’and ‘in relation to’ some cyclphilin and ‘is realized in’ only ‘cyclosporin a cyclophilin complex formation’)) that ‘has disposition’ some (‘to inhibit’ and ‘in relation to’ some calcineurin and ‘is realized in’ some ‘inhibition of calcineurin by cyclophilin-cyclosporin complex’) ‘cyclophilin’ subClassOf ‘protein’ that (‘has disposition’ some (‘to be part of complex’ and ‘in relation to’ some ‘cyclosporin a’ and ‘is realized in’ only ‘cyclosporin a cyclophilin complex formation’)) ‘cylcosporin a cyclophilin complex formation’ subClassOf ‘molecular complex formation’ that ‘has target’ some ‘cyclosporin a’ that ‘has target’ some ‘cyclophilin’ that ‘has product’ some ‘cyclophilin-cyclosporin a complex’ ‘cyclophilin-cyclosporin complex’ subClassOf ‘molecular complex’ that ‘has component part’ some ‘cyclophilin’ that ‘has component part’ some ‘cyclosporin a’ ‘inhibition of calcineurin by cyclophilin-cyclosporin a complex’ subClassOf ‘inhibition’ that ‘has agent’ some ‘cyclophilin-cyclosporin a complex’ and ‘results in’ some ‘decreased NF-AT dephosphorylation’ ‘decreased NF-AT dephosphorylation’ subClassOf ‘NF-At dephosphorylation’ that ‘has quality’ some (‘process rate’ that ‘is less than’ some (‘process rate’ that ‘is quality of’ some ‘NF-AT dephosphorylation’)) and ‘results in’ some ‘inhibition of interluekin-2 transcription’ ‘inhibition of interleukin-2 transcription’ subClassOf ‘inhibition’ ‘inhibition of T-Cell activation’ subClassOf ‘inhibition’ ‘mechanism of calcineurin inhibition by cyclosporin a’ subClassOf ‘mechanistic toxicology process specification’ that ‘has part’ some ‘cyclosporin a cyclophilin complex formation’ that ‘has part’ some ‘inhibition of calcineurin by cyclophilin-cyclosporin complex’ that ‘has part’ some ‘decreased NF-AT dephosphorylation’ that ‘has part’ some ‘inhibition of interleukin-2 transcription’ that ‘has part’ some ‘inhibition of T-cell activation’ that ‘has part’ some ‘immunosuppression’ and ‘cyclosporin a cyclophilin complex formation’ that precedes some (‘inhibition of calcineurin by cyclophilin-cyclosporin complex’ that preceeds some (‘decreased NF-AT dephosphorylation’ that precedes some (‘inhibition of interleukin-2 transcription’ and precedes some ‘inhibition of T-Cell activation’)))

Relation to Other Ontologies

References

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Notes

-Finish realization of dispositions for each entity in the use case