TLR-mediated modulation of micro-RNA profiling in human primary bronchial epithelial cells (P3003)
| Autor: | Becky Vonakis, Srinivas Sirimalle, Beverly Plunkett, Christopher Cheadle, Michele Ceccarelli, Fulvio D’Angelo, Paul Cox, El-Bdaoui Haddad, Cristiana Stellato |
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| Rok vydání: | 2013 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 190:114.2-114.2 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.190.supp.114.2 |
| Popis: | Global changes in miRNA expression in airway epithelium, a cell type critical in the mucosal response to microbial invasion, allergens and pollutants, have been only partially investigated. Cell stimulation with a TLR3 agonist ± cytokines was used to model disease-specific miRNA changes. PBEC (n=5) were cultured under air-liquid interface and treated with medium or polyI:C (1-10 μg/ml) ±TNFα/IFNγ (10 ng/ml each) for 24 hr. Total RNA was used for miRNA profiling (Agilent) and real-time-PCR analysis of inflammatory genes (control). PBEC supernatants were assayed using antibody arrays. Genome Ontology analysis was performed by Ingenuity pathway analysis. Expression of miR409-3p and miR624 was downregulated >30-fold compared to control following polyI:C treatment. Expression of 16 miRNAs was downregulated following polyI:C/TNFα/IFNγ treatment, with >30-fold reduction for miR617 and miR136 (calculated as Fold Change ≥ 1.5, p< 0.05 after Robust Multichip Average normalization). In cells challenged with the combined treatment, 145 genes (including 16 transcription factors) were predicted with high confidence (by 6/6 programs) as molecular targets for 6 of 16 differentially expressed miRNAs. PolyI:C plus TNFα/IFNγ strongly synergized in upregulating the mRNA and protein expression of CXCL8, GM-CSF, IL-6 and CCL2. The identification of the miRNA signature may identify new mechanisms of posttranscriptional gene control and generate new anti-inflammatory strategies. |
| Databáze: | OpenAIRE |
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