Asthmatic airway epithelium is intrinsically inflammatory and mitotically dyssynchronous.

摘要: Asthma is an inflammatory condition for which anti-inflammatory glucocorticoids are the standard of care. However, similar efficacy has not been shown agents targeting cells and pathways. This suggests a noninflammatory cell contributor (e.g., epithelium) to asthmatic inflammation. Herein, we sought define intrinsic glucocorticoid-affected properties airway epithelium compared with normal epithelium. Human primary differentiated epithelia were cultured in glucocorticoid-free medium beginning at -48 hours. They pulsed dexamethasone (20 nM) or vehicle 2 hours -26, -2, +22, +46 Cultures mechanically scrape-wounded 0 exposed continuously bromodeoxyuridine (BrdU). Cytokine secretions analyzed using cytometric bead assays. Wound regeneration/mitosis was by microscopy flow cytometry. Quiescent (n = 3) 6) showed minimal cytokine secretion mitotic indices. After wounding, secreted more basolateral TGF-β1, IL-10, IL-13, IL-1β (P < 0.05) regenerated less efficiently than (+48 h wound area reduction [mean ± SEM] 50.2 7.5% versus 78.6 7.7%; P 0.02). Asthmatic 40% fewer BrdU(+) +48 (0.32 0.05% 0.56 0.07% total cells; 0.03), those dyssynchronously distributed along cycle (52 10, 25 4, 23 7% G1/G0, S, G2/M, respectively) (71 1, 12 2, 17 2% respectively). Dexamethasone pulses improved epithelial inflammation regeneration/mitosis. In summary, show that inflammatory/fibrogenic correlated dyssynchronous mitosis upon injury. Intermittent simultaneously decreased resynchronized mitosis. These data, generated model lacking cells, support concept contributes