title: Interleukin-13, but not indomethacin, increases cysteinyl-leukotriene synthesis in human lung macrophages.
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 μM) 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.
authors: Infection, Inflammation and Immunity Division, University of Southampton School of Medicine, Southampton SO16 6YD, UK.
authors: Sarah E
authors: SE
authors: Jackson
authors: John W
authors: JW
authors: Holloway
authors: Jane A
authors: JA
authors: Warner
authors: Anthony P
authors: AP
authors: Sampson