Abstract
Allergic inflammation is primarily mediated by immune effector cells such as mast cells and basophils that release proinflammatory cytokines. Both mast cells and basophils are activated via their high affinity IgE receptor (FcεRI) which initiates the release of proinflammatory mediators such as histamine and tumor necrosis factor (TNF). Considerable effort has been focused on finding an effective basophil stabilizer that inhibits the activation of FcεRI-activated mediator release. Recently, eremophilane lactones, a novel family of sesquiterpene compound originally isolated from Petasites japonicas (Sieb. et Zucc.), have been described, and it has been postulated that they may have anti-inflammatory activity, particularly in allergic disease. Our objective was to determine the effect of two eremophilane lactones derived from 6β-angeloyloxy-3β,8-dihydroxyeremophil-7(11)-en-12,8β-olide (F-1) on immunoglobulin E (IgE)-dependent release of pro-inflammatory mediators by a basophil cell line, RBL-2H3, a model system for FcεRI-mediated activation of pro-inflammatory mediator release. The parent compound (F-1) was chemically modified to produce F-1a [6β-angeloyloxy-3β-benzoyloxy-8-hydroxyeremophil-7(11)-en-12,8β-olide] and F-1b [6β-ange...Continue Reading
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