Journal Article

Influenza A virus infection dysregulates the expression of microRNA-22 and its targets; CD147 and HDAC4, in epithelium of asthmatics

Williams, Teresa, Moheimani, Fatemeh, Hansbro, Philip M., Wark, Peter A., Knight, Darryl A., Reid, Andrew T., Koops, Jorinke

2018

Overview

Background Specific microRNAs (miRNAs) play essential roles in airway remodeling in asthma. Infection with influenza A virus (IAV) may also magnify pre-existing airway remodeling leading to asthma exacerbation. However, these events remain to be fully defined. We investigated the expression of miRNAs with diverse functions including proliferation (miR-20a), differentiation (miR-22) or innate/adaptive immune responses (miR-132) in primary bronchial epithelial cells (pBECs) of asthmatics following infection with the H1N1 strain of IAV. Methods pBECs from subjects ( n  = 5) with severe asthma and non-asthmatics were cultured as submerged monolayers or at the air-liquid-interface (ALI) conditions and incubated with IAV H1N1 (MOI 5) for up to 24 h. Isolated miRNAs were subjected to Taqman miRNAs assays. We confirmed miRNA targets using a specific mimic and antagomir. Taqman mRNAs assays and immunoblotting were used to assess expression of target genes and proteins, respectively. Results At baseline, these miRNAs were expressed at the same level in pBECs of asthmatics and non-asthmatics. After 24 h of infection, miR-22 expression increased significantly which was associated with the suppression of CD147 mRNA and HDAC4 mRNA and protein expression in pBECs from non-asthmatics, cultured in ALI. In contrast, miR-22 remained unchanged while CD147 expression increased and HDAC4 remained unaffected in cells from asthmatics. IAV H1N1 mediated increases in SP1 and c-Myc transcription factors may underpin the induction of CD147 in asthmatics. Conclusion The different profile of miR-22 expression in differentiated epithelial cells from non-asthmatics may indicate a self-defense mechanism against aberrant epithelial responses through suppressing CD147 and HDAC4, which is compromised in epithelial cells of asthmatics.

• Publisher: BioMed Central,BioMed Central Ltd,Nature Publishing Group,BMC
• Subject: Adaptive immunity / Airway remodeling / Asthma / Asthmatic persons / c-Myc protein / CD147 antigen / Cell culture / Cell differentiation / Dehydrogenases / Epithelial cells / Epithelium / Gene expression / Genes / Genetic aspects / Health aspects / Immune response / Immunoblotting / Infections / Influenza / Influenza A / Influenza A virus / Medicine / Medicine & Public Health / MicroRNA / MicroRNAs / miRNA / Myc protein / Pneumology/Respiratory System / Protein expression / Proteins / Regulation / Respiratory tract / Ribonucleic acid / RNA / Severe asthma / Software / Sp1 protein / Statistical analysis / Swine flu / Transcription factors / Viral infections / Viruses