RGD Reference Report - Molecular mechanisms of iNOS induction by IL-1 beta and IFN-gamma in rat aortic smooth muscle cells. - Rat Genome Database

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Molecular mechanisms of iNOS induction by IL-1 beta and IFN-gamma in rat aortic smooth muscle cells.

Authors: Teng, X  Zhang, H  Snead, C  Catravas, JD 
Citation: Teng X, etal., Am J Physiol Cell Physiol 2002 Jan;282(1):C144-52.
RGD ID: 619663
Pubmed: PMID:11742807   (View Abstract at PubMed)

In rat aortic smooth muscle cells (RASMC), interferon (IFN)-gamma enhanced nitrite accumulation and type II nitric oxide synthase (iNOS) protein expression induced by interleukin (IL)-1 beta. IFN-gamma alone had no effect on nitrite accumulation or iNOS protein. IL-1 beta, but not IFN-gamma, induced nuclear factor (NF)-kappa B and CCAAT box/enhancer binding protein (C/EBP) nuclear binding. Conversely, IFN-gamma, but not IL-1 beta, induced signal transducer and activator of transcription (STAT) 1 and interferon regulatory factor (IRF)-1 binding. In a -1.4-kb rat iNOS promoter segment, deletion of an IFN-gamma-activated site (GAS) increased IL-1 beta-induced activity but inhibited IFN-gamma-enhanced activity, suggesting a two-way effect of the GAS site on iNOS induction: enhancing induction through STAT1 activation and inhibiting induction through a non-IFN-gamma-mediated mechanism. Deletion of both an IRF and a C/EBP site reduced the IL-1 beta-induced and the IFN-gamma-enhanced activities. However, IRF site mutations decreased the IFN-gamma-enhanced activity without affecting the IL-1 beta-induced activity. Insertion of two IRF sites increased the IFN-gamma-enhanced, but not the IL-1 beta-induced, activity. Mutations of a reverse NF-kappa B site did not significantly change IFN-gamma-enhanced activity. We conclude that in RASMC, NF-kappa B and C/EBP mediate the IL-1 beta-induced iNOS expression, whereas IRF-1 and STAT1 mediate the IFN-gamma-enhanced iNOS induction.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Irf1Ratpositive regulation of transcription by RNA polymerase II  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Irf1  (interferon regulatory factor 1)


Additional Information