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Autor(en) / Beteiligte
Titel
NF-κB-mediated inhibition of microRNA-149-5p regulates Chitinase-3-like 1 expression in human airway epithelial cells
Ist Teil von
  • Cellular signalling, 2020-03, Vol.67, p.109498-109498, Article 109498
Ort / Verlag
England: Elsevier Inc
Erscheinungsjahr
2020
Quelle
Alma/SFX Local Collection
Beschreibungen/Notizen
  • Lower respiratory tract infections are among the most common causes of death worldwide. Main pathogens leading to these severe infections are viruses and gram-positive bacteria that activate toll-like receptor (TLR)-mediated immune responses via pathogen-associated molecular patterns. One protective factor induced during infection is Chitinase-3-like 1 (CHI3L1), which exerts various functions, e.g. in host cell proliferation and bacterial counteraction, and has been proposed as a biomarker in several acute and chronic inflammatory conditions. MicroRNAs (miR) have become important regulators of inflammation and infection and are considered therapeutic targets in recent years. However, it is not known whether microRNAs play a role in the regulation of CHI3L1 expression in TLR-mediated respiratory epithelial cell inflammation. In this study, we analysed the pre- and post-transcriptional regulation of CHI3L1 by TLRs in bronchial epithelial cells. Therefore, we stimulated BEAS-2B cells with the bacterial TLR2-ligand lipoteichoic acid or the viral dsRNA analogue poly(I:C). We observed an increase in the expression of CHI3L1, which was dependent on TNF-α-mediated NF-κB activation in TLR2- and TLR3-activated cells. Moreover, TLR2 and − 3 stimulation caused downregulation of the microRNA miR-149-5p, an effect that could be suppressed by inhibiting NF-κB translocation into the nucleus. Luciferase reporter assays identified a direct interaction of miR-149-5p with the CHI3L1 3´untranslated region. This interaction was confirmed by inhibition and overexpression of miR-149-5p in BEAS-2B cells, which altered the expression levels of CHI3L1 mRNA. In summary, miR-149-5p directly regulates CHI3L1 in context of TLR-mediated airway epithelial cell inflammation and may be a potential therapeutic target in inflammation and other diseases. [Display omitted] •Activation of TLR2 and TLR3 increases CHI3L1 and down-regulates miR-149-5p in bronchial epithelial cells.•Both changes are dependent on TNF-α-mediated NF-κB translocation to the nucleus.•miR-149-5p directly targets CHI3L1 3‵untranslated region.•Absence or presence of miR-149-5p function alters expression levels of CHI3L1.
Sprache
Englisch
Identifikatoren
ISSN: 0898-6568
eISSN: 1873-3913
DOI: 10.1016/j.cellsig.2019.109498
Titel-ID: cdi_proquest_miscellaneous_2327367003

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