title: Down-Regulation of miR-146a Expression Induces Allergic Conjunctivitis in Mice by Increasing TSLP Level.
abstract: BACKGROUND
  Pollen is the most common aeroallergen to cause conjunctivitis. In this study, we established a short ragweed (SRW)-induced mouse model of allergic conjunctivitis (AC) and aimed to explore the potential role of miR-146a and its downstream molecules in the development of ocular allergic inflammation.
  
  
  METHODS
  The mouse model of challenge pollen was used for in vivo study. The culture model of primary human limbal epithelium (HLE) exposed to lipopolysaccharide (LPS) was performed for in vitro research. The numbers of eosinophils and total inflammatory cells were examined using Giemsa staining. The expression of mRNA and miR-146a was determined by quantitative RT-PCR, and protein production was evaluated by Western blotting.
  
  
  RESULTS
  In vivo of mice, pollen challenge induced conjunctiva inflammatory response indicated by increased number of eosinophils and total inflammatory cells. Interestingly, pollen significantly attenuated miR-146a expression while it enhanced expression of thymic stromal lymphopoietin (TSLP) and its downstream molecules, including TSLP receptor (TSLPR)/ OX40 ligand (OX40L) /CD11C. In vitro of HCE, downregulation effect of miR-146a expression induced by LPS was reversed by Bay treatment, an inhibitor for nuclear factor kappa B (NF-κB), and LPS-induced cell inflammation is mediated by miR-146a-TSLP/TSLPR/OX40L/CD11C signaling pathway. This was further demonstrated by overexpression of miR-146a in mouse abrogated pollen-triggered conjunctiva inflammatory reaction as well as pollen-induced activity of TSLP/TSLPR/OX40L/CD11C signaling.
  
  
  CONCLUSIONS
  Down-regulation of miR-146a expression induces allergic conjunctivitis in mice by increasing TSLP level.
authors.affiliation: Department of Ophthalmology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China (mainland).
authors.forename: Wen
authors.initials: W
authors.lastname: Sun
authors.affiliation: Department of Ophthalmology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China (mainland).
authors.forename: Yan
authors.initials: Y
authors.lastname: Sheng
authors.affiliation: Department of Ophthalmology, Navy General Hospital, Beijing, China (mainland).
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Ophthalmology, Xin Hua Hospital of Zhejiang Province, Hangzhou, Zhejiang, China (mainland).
authors.forename: Dong
authors.initials: D
authors.lastname: Xu
authors.affiliation: Department of Ophthalmology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China (mainland).
authors.forename: Yangshun
authors.initials: Y
authors.lastname: Gu
mesh_terms: D000818:Animals; D003233:Conjunctivitis, Allergic / Q000235:genetics*; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D015536:Down-Regulation; D019573:Epithelium, Corneal / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics*; D016328:NF-kappa B / Q000378:metabolism; D011058:Pollen; D015398:Signal Transduction; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; D035683:MicroRNAs; C534190:Mirn146 microRNA, mouse; D016328:NF-kappa B; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse