A long noncoding RNA antisense to ICAM-1 is involved in allergic asthma associated hyperreactive response of airway epithelial cells.
A long noncoding RNA antisense to ICAM-1 is involved in allergic asthma associated hyperreactive response of airway epithelial cells.
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DOI：
10.1038/s41385-020-00352-9
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发表时间：
2021-05
影响因子：
8
通讯作者：
Chand HS
中科院分区：
文献类型：
--
作者：
Devadoss D;Daly G;Manevski M;Houserova D;Hussain SS;Baumlin N;Salathe M;Borchert GM;Langley RJ;Chand HS
传导气道的上皮细胞是抵抗空气传播病原体和过敏原的关键第一道防线，这些病原体和过敏原协调炎症反应和纤毛粘膜清除。然而，与过敏性哮喘相关的上皮高反应性的分子机制尚不完全清楚。在体外气液界面（ALI）分化的人气道上皮细胞（HAECs）的转录组学分析显示，725个差异表达的即时早期转录物，包括假定的长链非编码rna （lncRNAs）。在ICAM-1或LASI的反义链上发现了一个新的lncRNA，该lncRNA与粘蛋白MUC5AC及其转录调节因子SPDEF一起在lps引物的haec中诱导。LPS引发的LASI、MUC5AC和SPDEF转录物在离体培养的哮喘haec中表达较高，LPS处理进一步增强了这些细胞的表达。多荧光原位杂交和免疫染色显示黏液负荷增加的哮喘患者气道切片MUC5AC+杯状细胞LASI表达升高。LPS或il -13诱导的LASI转录本主要富集于核/核周区域，并与ICAM-1、IL-6和CXCL-8表达增加相关。阻断LASI表达可降低LPS或il -13诱导的上皮炎症因子和muc5ac表达，提示新型lncRNA LASI可能在过敏性哮喘中LPS引发的气道上皮反应失调中发挥关键作用。
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 andMUC5AC 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.
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DOI：
10.1056/nejmra0910061
发表时间：
2010-12-02
期刊：
The New England journal of medicine
影响因子：
--
作者：
Fahy JV;Dickey BF
通讯作者：
Dickey BF
影响因子：
8.3
作者：
Benam, Kambez H.;Vladar, Eszter K.;Evans, Christopher M.
通讯作者：
Evans, Christopher M.
影响因子：
9.6
作者：
Mitchell, Patrick D.;O'Byrne, Paul M.
通讯作者：
O'Byrne, Paul M.
影响因子：
13.6
作者：
Long Y;Wang X;Youmans DT;Cech TR
通讯作者：
Cech TR
影响因子：
14.9
作者：
Edgar, R;Domrachev, M;Lash, AE
通讯作者：
Lash, AE