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Alveolar macrophages (AMs) contribute to airway inflammation and remodeling in allergic asthma. Calcaratarin D (CalD), a labdane diterpenoid isolated from the rhizomes of the medicinal plant Alpinia calcarata, has recently been shown to possess anti-inflammatory properties. The present study evaluated protective effects of CalD in a house dust mite (HDM)-induced asthma mouse model.The effects of CalD on AMs in contributing to anti-inflammatory effects in asthma were investigated through a series of in vivo, ex vivo and in vitro experiments.CalD reduced bronchoalveolar lavage fluid total and differential cell counts, serum IgE levels, mucus hypersecretion and airway hyperresponsiveness in HDM-challenged mice. Besides, CalD abrogated a wide array of pro-inflammatory cytokines and chemokines, and oxidative damage markers in isolated lung tissues. CalD suppressed HDM-induced increase in Arg1 (M2 marker) in AMs from lung tissues, and reduced lung polyamine levels. CalD weakened antigen presentation capability of AMs by abating CD80 expression, reduced AM-derived CCL17 and CCL22 levels, and lessened Th2 cytokines from CD4Our results demonstrated for the first time that CalD is a novel anti-inflammatory natural compound for allergic asthma by modulating AM functions. |
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