DsRNA induction of microRNA-155 disrupt tight junction barrier by modulating claudins
Hisato Hiranuma1, Yasuhiro Gon1, Shuichiro Maruoka1
1Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan.
Background:
The impaired barrier function of the airway epithelium due to RNA virus infection is closely related to the development and exacerbation of allergic airway inflammation.
Objective:
In this study, we investigated the roles of microRNAs on the mechanisms of double-stranded RNA (dsRNA)-induced epithelial barrier dysfunction.
Methods:
16HBE14o- human bronchial epithelial cells were grown to confluence on Transwell inserts and exposed to poly-I:C. We studied epithelial barrier function by measuring transepithelial electrical resistance and paracellular flux of fluorescent markers and structure of tight junctions by immunofluorescence microscopy.
Results:
Poly-I:C treated 16HBE14o- cells increased paracellular permeability. Knockdown of Toll-like receptor 3 and TRIF abrogated these effects. The expression of microRNA-155 (miR-155) was increased by poly-I:C in dose-dependent manner. Transfection of mir155 mimics into 16HBE14o- cells increased permeability and inhibited tight junction formation. Transfection of miR-155 inhibitor suppressed poly-I:C-induced barrier disruption. Poly-I:C treatment significantly decreased the expression of claudin members-claudin-1, -3, -4, -5, -9, -11, -16, -18 and -19. Transfection of miR-155 mimics showed similar changing expression pattern of claudin members with those of poly-I:C treatment.
Conclusion:
These results suggest that RNA virus infection can impair the epithelial barrier disruption mechanism by down-regulation of claudin members through the induction of miR-155.
Insights
RNA virus infection impairs airway epithelial barrier function by increasing microRNA-155 (miR-155). This leads to reduced claudin expression, exacerbating allergic airway inflammation.
Area of Science:
- Immunology
- Molecular Biology
- Respiratory Medicine
Background:
- RNA virus infections compromise airway epithelial barrier integrity.
- This compromised barrier function is linked to allergic airway inflammation development and worsening.
Purpose of the Study:
- To investigate microRNA roles in double-stranded RNA (dsRNA)-induced epithelial barrier dysfunction.
- To elucidate the mechanism by which dsRNA affects epithelial barrier function.
Main Methods:
- Human bronchial epithelial cells (16HBE14o-) were exposed to poly-I:C, a dsRNA mimic.
- Epithelial barrier function was assessed via transepithelial electrical resistance and paracellular flux.
- Tight junction structures were analyzed using immunofluorescence microscopy.
Main Results:
- Poly-I:C exposure increased cell permeability and disrupted tight junctions.
- MicroRNA-155 (miR-155) expression was upregulated by poly-I:C in a dose-dependent manner.
- miR-155 mimics increased permeability and inhibited tight junctions, while miR-155 inhibitors reversed poly-I:C effects. Poly-I:C and miR-155 mimics decreased claudin expression.
Conclusions:
- RNA virus infection impairs epithelial barrier function by inducing miR-155.
- This induction leads to the downregulation of claudin members, contributing to barrier disruption.
- Targeting miR-155 may offer a therapeutic strategy for RNA virus-induced airway inflammation.
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