Stimulation of Ciliary Activity by Indomethacin in Rabbit Tracheal Epithelial Organ Culture

Abstract

Inflammatory mediators influence mucociliary transport function in the lung, which may be dependent on the beating of the underlying cilia. To determine whether a nonsteroidal anti-inflammatory drug affects this function, and, if so, what is the mechanism action, we examined the effect of indomethacin on ciliary beat frequency (CBF) of cultured rabbit tracheal epithelial cells by a photoelectric technique. Addition of indomethacin dose-dependently enhanced CBF without any ciliary disco-ordination, the maximal increase and K_m being 26.5 ± 4.8% (mean ± SE, p < 0.001) and 6.8 × 10^-7M, respectively. Pretreatment of tissues with nordihydroguaretic acid (10^-5M), an inhibitor of the lipoxygenase pathway, did not change the baseline CBF, but inhibited the response of CBF to 3 × 10^-6M indomethacin (p < 0.01). These results suggest that indomethacin may accelerate mucociliary clearance through the augmentation of ciliary motility and that this ciliostimulation may be mediated by leukotrienes produced by activation of the lipoxygenase pathway of arachidonic acid metabolism

Effects of Prostacyclin and Beraprost on Ciliary Motilit&gamma; of Rabbit Airway Epithelium

“…In the present study, incubation of cells with the cyclooxygenase inhibitor indometacin per se increased CBF, as has been described previously [21], However, none of the blockers, including the p-adrenergic recep tor antagonist propranolol, indometacin and the lipoxygenase inhibitor AA-861 [9], altered the increase in CBF in response to prostacy clin and beraprost. Thus, possible contribu tions of these factors seem to be unlikely.…”

“…Ciliary motility of airway epithelium can be regulated by a number of factors including p-adrenergic receptor [3], arachidonic acid metabolites [21,22], and protein kinase A [13], Because p-adrenergic receptors are present on airway epithelial cells and because this cell type synthesizes and releases PGs and leukotrienes, the effects of prostacyclin and beraprost could be mediated by these pro cesses. In the present study, incubation of cells with the cyclooxygenase inhibitor indometacin per se increased CBF, as has been described previously [21], However, none of the blockers, including the p-adrenergic recep tor antagonist propranolol, indometacin and the lipoxygenase inhibitor AA-861 [9], altered the increase in CBF in response to prostacy clin and beraprost.…”