microRNA-181b is increased in cystic fibrosis cells and impairs lipoxin A4 receptor-dependent mechanisms of inflammation resolution and antimicrobial defense.
Articolo
Data di Pubblicazione:
2017
Abstract:
The involvement of microRNA (miR) in cystic fibrosis (CF) pathobiology is rapidly emerging. We
previously documented that miR-181b controls the expression of the ALX/FPR2 receptor, which is
recognized by the endogenous proresolution ligand, lipoxin (LX)A4. Here, we examined whether the
miR-181b-ALX/FPR2 circuit was altered in CF. We examined human airways epithelial cells, normal
(16HBE14o-), carrying the ΔF508 mutation (CFBE41o-) or corrected for this mutation (CFBE41o-/
CEP-CFTR wt 6.2 kb), as well as monocyte-derived macrophages (MΦs) from CF patients. CFBE41ocells
exhibited higher miR-181b and reduced ALX/FPR2 levels compared to 16HBE14o- and CFBE41o-/
CEP-CFTR wt 6.2 kb cells. An anti-mir-181b significantly enhanced ALX/FPR2 expression (+ 60%) as
well as LXA4-induced increase in transepithelial electric resistance (+ 25%) in CFBE41o- cells. MΦs
from CF patients also displayed increased miR-181b (+ 100%) and lower ALX/FPR2 levels (− 20%)
compared to healthy cells. An anti-mir-181b enhanced ALX/FPR2 expression (+ 40%) and normalized
receptor-dependent LXA4-induced phagocytosis of fluorescent-labeled zymosan particles as well
as of Pseudomonas aeruginosa by CF-MΦs. These results provide the first evidence that miR-181b
is overexpressed in CF cells, impairing some mechanisms of the ALX/FPR2-dependent pathway
of inflammation resolution. Thus, targeting miR-181b may represent a strategy to enhance antiinflammatory
and anti-microbial defense mechanisms in CF.
Tipologia CRIS:
1.1 Articolo in rivista
Elenco autori:
Pierdomenico, ANNA MARIA; Patruno, Sara; Codagnone, Marilina; Simiele, Felice; Veronica Cecilia, Mari; Plebani, Roberto; Recchiuti, Antonio; Romano, Mario
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