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• W2322202289 abstract "Background Aspirin-exacerbated respiratory disease (AERD) is explained in part by overexpression of 5-lipoxygenase and leukotriene C 4 synthase (LTC 4 S), resulting in constitutive overproduction of cysteinyl leukotrienes (CysLTs) and driving the surge in CysLT production that occurs with aspirin ingestion. Similarly, AERD is characterized by the overexpression of CysLT receptors. Increased levels of both interleukin (IL)-4 and interferon (IFN)-y are present in the tissue of AERD subjects. Previous studies demonstrated that IL-4 is primarily responsible for the up-regulation of LTC 4 S by mast cells. Methods Literature review. Results Our previous studies demonstrated that IFN-γ, but not IL-4, drives this process in eosinophils. These published studies also extend to both IL-4 and IFN-γ the ability to up-regulate CysLT receptors. Prostaglandin E 2 (PGE 2 ) acts to prevent CysLT secretion by inhibiting mast cell and eosinophil activation. PGE 2 concentrations are reduced in AERD, and our published studies confirm that this reflects diminished expression of cyclooxygenase (COX)-2. A process again that is driven by IL-4. Thus, IL-4 and IFN-γ together play an important pathogenic role in generating the phenotype of AERD. Finally, induction of LTC 4 S and CysLT1 receptors by IL-4 reflects in part the IL-4-mediated activation of signal transducer and activator of transcription 6 (STAT6). Our previous studies demonstrated that aspirin blocks trafficking of STAT6 into the nucleus and thereby prevents IL-4-mediated induction of these transcripts, thereby suggesting a modality by which aspirin desensitization could provide therapeutic benefit for AERD patients. Conclusion This review will examine the evidence supporting this model." @default.
• W2322202289 created "2016-06-24" @default.
• W2322202289 creator A5063948687 @default.
• W2322202289 creator A5079959172 @default.
• W2322202289 date "2015-01-01" @default.
• W2322202289 modified "2023-10-10" @default.
• W2322202289 title "Factors Driving the Aspirin Exacerbated Respiratory Disease Phenotype" @default.
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• W2322202289 doi "https://doi.org/10.2500/ajra.2015.29.4123" @default.
• W2322202289 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4288232" @default.
• W2322202289 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25590316" @default.
• W2322202289 hasPublicationYear "2015" @default.
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