Abstract
Purpose: :
ST2 gene encodes both membrane–bound IL–1 receptor–related protein (ST2L) and soluble form (sST2) with distinctive promoters. ST2L protein is known as a functional marker for Th2 cells and an IL18–like cytokine IL33 was very recently identified as a ligand for ST2L. IL33 elicit eosinophilic inflammation and induce Th2 cytokine expression. To clarify the role of ST2 during ocular surface inflammation, we have examined ST2 expression in both cornea and conjunctiva, as well as in various ocular surface diseases.
Methods: :
ST2 and IL33 expression in corneal cells, conjunctival cells, and mast cells were examined by RT–PCR and immunoblotting. ST2 expression in various ocular surface disorders was examined by immunohistochemistry. The reporter gene assay of ST2 promoter regions were performed with human corneal epithelial cells.
Results: :
sST2 expression was detected in human corneal and conjunctival cells. ST2L (IL33 receptor) expression was observed in human PBMC and mast cells. IL33 mRNA expression was observed in human corneal and conjunctival cells. Immunohistochemical analysis showed sST2 protein expression in the conjunctival epithelium of Stevens Johnson Syndrome and Ocular Cicatricial Pemphigoid, but not in normal adult conjunctival epithelium. ST2 expression was also observed at the mast cells of subconjunctival tissue. Human corneal cells used the proximal ST2 promoter exclusively, which regulates the transcription of sST2.
Conclusions: :
Human ocular surface epithelium produces a proinflammatory cytokine IL33 and its soluble receptor sST2. The sST2 protein may act as a decoy receptor to inhibit IL33 induced inflammation on the eye surface.
Keywords: inflammation • cornea: epithelium • conjunctiva