Epithelial cells of the conducting airways are a pivotal first line of defense against airborne pathogens and allergens that orchestrate inflammatory responses and mucociliary clearance. Nonetheless, the molecular mechanisms responsible for epithelial hyperreactivity associated with allergic asthma are not completely understood. Transcriptomic analysis of human airway epithelial cells (HAECs), differentiated in-vitro at air-liquid interface (ALI), showed 725 differentially expressed immediate-early transcripts, including putative long noncoding RNAs (lncRNAs). A novel lncRNA on the antisense strand of ICAM-1 or LASI was identified, which was induced in LPS-primed HAECs along with mucin MUC5AC and its transcriptional regulator SPDEF. LPS-primed expression of LASI, MUC5AC, and SPDEF transcripts were higher in ex-vivo cultured asthmatic HAECs that were further augmented by LPS treatment. Airway sections from asthmatics with increased mucus load showed higher LASI expression in MUC5AC⁺ goblet cells following multi-fluorescent in-situ hybridization and immunostaining. LPS- or IL-13-induced LASI transcripts were mostly enriched in the nuclear/perinuclear region and were associated with increased ICAM-1, IL-6, and CXCL-8 expression. Blocking LASI expression reduced the LPS or IL-13-induced epithelial inflammatory factors and MUC5AC expression, suggesting that the novel lncRNA LASI could play a key role in LPS-primed trained airway epithelial responses that are dysregulated in allergic asthma.

传导气道的上皮细胞是抵御空气传播的病原体和过敏原的关键第一道防线，可协调炎症反应和粘膜纤毛清除。尽管如此，与过敏性哮喘相关的上皮过度反应的分子机制尚不完全清楚。人气道上皮细胞 (HAEC) 的转录组学分析在气液界面 (ALI) 体外分化，显示 725 个差异表达的即刻早期转录本，包括推定的长链非编码 RNA (lncRNA)。在I CAM-1 或LASI的反义链上鉴定了一种新的 lncRNA，它与粘蛋白MUC5AC一起在 LPS 引发的 HAEC 中被诱导及其转录调节因子SPDEF。LPS 引发的LASI、MUC5AC和SPDEF转录物的表达在离体培养的哮喘 HAECs 中更高，并通过 LPS 处理进一步增强。多荧光原位杂交和免疫染色后，粘液负荷增加的哮喘患者的气道切片显示MUC5AC ^{+杯状细胞中有更高的}LASI表达。LPS 或 IL-13 诱导的LASI转录物主要富集在核/核周区域，并且与ICAM-1、IL-6和CXCL-8表达增加有关。阻塞LASI表达降低了 LPS 或 IL-13 诱导的上皮炎症因子和MUC5AC表达，表明新型 lncRNA LASI可能在 LPS 引发的训练气道上皮反应中发挥关键作用，这些反应在过敏性哮喘中失调。