LL-37 and Double-Stranded RNA Synergistically Upregulate Bronchial Epithelial TLR3 Involving Enhanced Import of Double-Stranded RNA and Downstream TLR3 Signaling.
Biomedicines
; 10(2)2022 Feb 19.
Article
in En
| MEDLINE
| ID: mdl-35203701
ABSTRACT
The human host defense peptide LL-37 influences double-stranded RNA signaling, but this process is not well understood. Here, we investigate synergistic actions of LL-37 and synthetic double-stranded RNA (poly IC) on toll-like receptor 3 (TLR3) expression and signaling, and examine underlying mechanisms. In bronchial epithelial BEAS-2B cells, LL-37 potentiated poly IC-induced TLR3 mRNA and protein expression demonstrated by qPCR and Western blot, respectively. Interestingly, these effects were associated with increased uptake of rhodamine-tagged poly IC visualized by immunocytochemistry. The LL-37/poly IC-induced upregulation of TLR3 mRNA expression was prevented by the endosomal acidification inhibitor chloroquine, indicating involvement of downstream TLR3 signaling. The glucocorticoid dexamethasone reduced LL-37/poly IC-induced TLR3 expression on both mRNA and protein levels, and this effect was associated with increased IκBα protein expression, suggesting that dexamethasone acts via attenuation of NF-κB activity. We conclude that LL-37 potentiates poly IC-induced upregulation of TLR3 through a mechanism that may involve enhanced import of poly IC and that LL-37/poly IC-induced TLR3 expression is associated with downstream TLR3 signaling and sensitive to inhibition of NF-κB activity.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
Biomedicines
Year:
2022
Document type:
Article
Affiliation country:
Sweden