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Invest Ophthalmol Vis Sci ; 61(3): 8, 2020 03 09.
Article in English | MEDLINE | ID: mdl-32150250

ABSTRACT

Purpose: Thymic stromal lymphopoietin (TSLP) is a pro-allergic cytokine that initiates allergic inflammatory reaction between epithelial and dendritic cells (DCs). miR-19b was reported to suppress TSLP expression. The present study aimed to examine miR-19b expression, regulation, and function in allergic conjunctivitis (AC). Methods: A murine model of experimental AC was induced in BALB/c mice by short ragweed pollen. The serum, eye balls, conjunctiva, and cervical lymph nodes (CLN) were used for the study. Gene expression was determined by RT-PCR, whereas protein production and activation were evaluated by immunostaining, ELISA, and Western blotting. Results: In the murine AC model, miR-19b was aberrantly downregulated, whereas the levels of TSLP and p-STAT3, as well as the number of CD11c+ pSTAT3+ DCs were increased. Moreover, Th2 inflammatory cytokine expression was significantly increased. These severe phenotypes could be counteracted by either applying exogenous miR-19b mimic microRNAs or the JAK/STAT inhibitor CYT387. Moreover, overexpression of miR-19b repressed p-STAT3 expression and the number of CD11c+ cells in AC eye and CLN tissues. Conclusions: These findings suggested that miR-19b reduced ocular surface inflammation by inhibiting Stat3 signaling via TSLP downregulation in a murine AC model. Moreover, the present study further demonstrated the clinical potential of applying miR-19b and anti-JAK/STAT therapies in the treatment of AC.


Subject(s)
Conjunctivitis, Allergic/genetics , Janus Kinases/physiology , MicroRNAs/genetics , STAT Transcription Factors/physiology , Animals , Antigens, Plant , CD11 Antigens/metabolism , Cervical Vertebrae , Conjunctiva/metabolism , Conjunctivitis, Allergic/immunology , Conjunctivitis, Allergic/metabolism , Cornea/metabolism , Cytokines/biosynthesis , Disease Models, Animal , Down-Regulation , Female , Janus Kinases/antagonists & inhibitors , Lymph Nodes/metabolism , Mice, Inbred BALB C , MicroRNAs/biosynthesis , Phenotype , Plant Extracts , STAT Transcription Factors/antagonists & inhibitors , STAT3 Transcription Factor/metabolism , Signal Transduction , Thymic Stromal Lymphopoietin
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