Interleukin-13, but not indomethacin, increases cysteinyl-leukotriene synthesis in human lung macrophages

Jackson, Sarah E., Holloway, John W., Warner, Jane A. and Sampson, Anthony P. (2011) Interleukin-13, but not indomethacin, increases cysteinyl-leukotriene synthesis in human lung macrophages. Journal of Allergy, 2012, 1-6. (doi:10.1155/2012/348741). (PMID:22121385)

Abstract

Aspirin-exacerbated respiratory disease (AERD) is associated with constitutively elevated synthesis of bronchoconstrictor cysteinyl-leukotrienes, associated with increased expression of leukotriene (LT)C(4) synthase and Th2 cytokines and airway eosinophilia. We examined whether interleukin-13 can increase LTC(4) synthase gene transcription and cysteinyl-leukotriene synthesis in macrophages isolated from resected human lung tissue and whether an NSAID (indomethacin) can trigger further cysteinyl-leukotriene synthesis in these cells. Overnight culture of human lung macrophages with IL-13 (10?ng/mL) increased spontaneous and ionophore-stimulated production of cysteinyl-leukotrienes by 42% (P = 0.02) and 52% (P = 0.005), respectively, as quantified by enzyme immunoassays, but PCR gene transcription assays did not demonstrate an effect on LTC4S mRNA. The addition of indomethacin (100??M) did not modulate cysteinyl-leukotriene production in either IL-13-treated or untreated macrophages. We conclude that while IL-13 enhances cysteinyl-leukotriene synthesis in human lung macrophages, it does not replicate the enhanced LTC(4) synthase expression observed in the AERD lung nor confer sensitivity to NSAIDs

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Contributors

Author: John W. Holloway

Author: Anthony P. Sampson

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