title: Regulation of interleukin 33/ST2 signaling of human corneal epithelium in allergic diseases.
abstract: OBJECTIVE
  To identify the function of ST2 and explore the role of IL-33/ST2 signaling in regulating the pro-allergic cytokine production in human corneal epithelial cells (HCECs).
  
  
  METHODS
  Human corneal tissues and cultured primary HCECs were treated with IL-33 in different concentrations without or with different inhibitors to evaluate the expression, location and signaling pathways of ST2 in regulating production of pro-allergic cytokine and chemokine. The expression of mRNA was determined by reverse transcription and real time PCR, and protein production was measured by enzyme-linked immunosorbent assay (ELISA), immunohistochemical and immunofluorescent staining. ST2 protein was detected in donor corneal epithelium, and ST2 signal was enhanced by exposure to IL-33.
  
  
  RESULTS
  IL-33 significantly stimulated production of pro-allergic cytokines thymic stromal lymphopoietin (TSLP) and chemokine (CCL2, CCL20, CCL22) in HCECs at both mRNA and protein levels. These stimulated productions of pro-allergic mediators by IL-33 were blocked by ST2 antibody or soluble ST2 protein (P<0.05). Interestingly, the IκB-α inhibitor BAY11-7082 or NF-κB activation inhibitor quinazoline blocked NF-κB p65 protein nuclear translocation, and also suppressed the productions of these pro-allergic cytokines and chemokine induced by IL-33.
  
  
  CONCLUSIONS
  These findings demonstrate that IL-33/ST2 signaling plays an important role in regulating IL-33 induced pro-allergic responses. IL-33 and ST2 could become novel molecular targets for the intervention of allergic diseases in ocular surface.
authors.affiliation: Department of Ophthalmology, the Affiliated Hospital of Medical College, Qingdao University, Qingdao 266003, Shandong Province, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Lin
authors.forename: Gui-Qiu
authors.initials: GQ
authors.lastname: Zhao
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xu
authors.forename: Cheng-Ye
authors.initials: CY
authors.lastname: Che
authors.forename: Li-Ting
authors.initials: LT
authors.lastname: Hu
authors.forename: Nan
authors.initials: N
authors.lastname: Jiang
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Zhang
keywords: NF-κB; ST2; allergic diseases; cornea; epithelium; human; interleukin 33
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