TLR-mediated modulation of micro-RNA profiling in human primary bronchial epithelial cells (P3003)
2013; American Association of Immunologists; Volume: 190; Issue: 1_Supplement Linguagem: Inglês
10.4049/jimmunol.190.supp.114.2
ISSN1550-6606
AutoresBecky M. Vonakis, Srinivas Sirimalle, Beverly Plunkett, Christopher Cheadle, Michele Ceccarelli, Fulvio D’Angelo, Paul Alan Cox, El‐Bdaoui Haddad, Cristiana Stellato,
Tópico(s)RNA modifications and cancer
ResumoAbstract 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.
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