期刊
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
卷 50, 期 6, 页码 1144-1155出版社
AMER THORACIC SOC
DOI: 10.1165/rcmb.2013-0160OC
关键词
microRNA; inflammation; lung; cystic fibrosis
资金
- Fondazione Cariparo (Cassa di Risparmio di Padova e Rovigo)
- Consorzio Interuniversitario di Biotecnologie (CIB)
- Telethon [GGP10214]
- Italian Cystic Fibrosis Research Foundation [FFC 17 2010, FFC 19/2011, FFC 1 2012]
- Associazione Italiana Ricerca sul Cancro (AIRC) [IG13575]
- Associazione Veneta per la Lotta alla Talassemia (AVLT)
- CIB fellowship
- [COFIN-2009]
In this study we analyzed the microRNA profile of cystic fibrosis (CF) bronchial epithelial IB3-1 cells infected with Pseudomonas aeruginosa by microarray and quantitative RT-PCR, demonstrating that microRNA 93 (miR-93), which is highly expressed in basal conditions, decreases during infection in parallel with increased expression of the IL-8 gene. The down-regulation of miR-93 after P. aeruginosa infection was confirmed in other bronchial cell lines derived from subjects with and without CF, namely CuFi-1 and NuLi-1 cells. Sequence analysis shows that the 3 '-UTR region of IL-8 mRNA is a potential target of miR-93 and that the consensus sequence is highly conserved throughout molecular evolution. The possible involvement of miR-93 in IL-8 gene regulation was validated using three luciferase vectors, including one carrying the complete 3 '-wUTR region of the IL-8mRNA and one carrying the same region with a mutated miR-93 site. Up-modulation of IL-8 after P. aeruginosa infection was counteracted in IB3-1, CuFi-1, and NuLi-1 cells by pre-miR-93 transfection. In addition, IL-8 was up-regulated in uninfected cells treated with antagomiR-93. Our results support the concept of a possible link between microRNA expression and IL-8 induction in bronchial epithelial cells infected with P. aeruginosa. Specifically, the data presented here indicate that, in addition to NF-kappa B-dependent up-regulation of IL-8 gene transcription, IL-8 protein expression is posttranscriptionally regulated by interactions of the IL-8 mRNA with the inhibitory miR-93.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据