Abstract
Purpose: :
Interleukin-33 (IL-33) is a novel cytokine, inducing prominent Th2 dominant, eoshinophilic inflammation in the lungs and skin. Recently, the IL-33 hetero-dimmer receptor was identified as ST2L, one of the atopy related molecules, and as IL-1 receptor beta. We previously reported IL-33 mRNA expression in human corneal and conjunctival epithelium (ARVO, 2006). We investigated the regulation of IL-33 expression and its down-stream signaling pathway in human ocular surface epithelium.
Methods: :
The expression of IL-33 mRNA in human corneal epithelial cells (HCE) was quantified with real-time PCR with various inflammatory stimuli. The effect of recombinant IL-33 (rIL-33) on HCE was examined by phospho-p38 MAPK expression. The intensity of the NF-kB signal was quantified with luciferase assay using HCE, with IL-33 receptor (ST2L) over-expression or its decoy receptor (soluble ST2: sST2) over-expression.
Results: :
Constitutive IL-33 mRNA expression was observed in HCE cells and its expression was up-regulated with interferon gamma stimulation. rIL-33 stimulation induced phospholylation of p38 MAPK, and increased NF-kB signals in HCE. ST2L over-expression enhanced NF-kB signals in HCE, whereas sST2 over-expression blocked NF-kB activation signals through IL-33 stimulation.
Conclusions: :
IL-33 stimulation activates HCE through the p38 MAPK and NF-kB pathways. The soluble ST2 molecule is a counter regulatory molecule for this pathway like the IL-1 receptor agonist for IL-1 pathways.
Keywords: cornea: basic science • cornea: epithelium • cytokines/chemokines