Abstract
Interleukin (IL) 33 has been recently identified as a ligand to the ST2 receptor that mediates Th2-dominant allergic inflammation. The purpose of this study was to explore the role of toll-like receptor (TLR)-mediated innate immunity in IL-33 induction by mucosal epithelium. Human corneal tissues and cultured primary human corneal epithelial cells (HCECs) were treated with a variety of viral or bacterial components without or with different inhibitors to evaluate the IL-33 regulation and signaling pathways. The level of mRNA expression was determined by reverse transcription and real time PCR, and protein was measured by ELISA, immunostaining and Western blotting. IL-33 mRNA and protein were largely induced by various microbial components, mainly by polyI:C and flagellin, the ligands to TLR3 and TLR5, respectively in human corneal epithelium ex vivo and in vitro cultures. Pro-IL-33 protein was normally restricted inside cells, and could be secreted outside when activated by ATP. The PolyI:C induced IL-33 production was blocked by TLR3 antibody or TRIF Inhibitory peptide, while flagellin stimulated IL-33 was blocked by TLR5 antibody or MyD88 Inhibitory peptide. Interestingly, IκB-α inhibitor (BAY11-7082) or NF-κB inhibitor (quinazoline) blocked NF-κB p65 protein nuclear translocation, and suppressed IL-33 production induced by PolyI:C and flagellin. These findings demonstrate that IL-33, an epithelium-derived pro-allergic cytokine, is induced by microbial ligands through TLR-mediated innate signaling pathways, suggesting a possible role of mucosal epithelium in Th2-dominant allergic inflammation.
Original language | English (US) |
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Pages (from-to) | 1383-91 |
Number of pages | 9 |
Journal | International Journal of Biochemistry and Cell Biology |
Volume | 43 |
Issue number | 9 |
DOIs | |
State | Published - Sep 2011 |
Externally published | Yes |
Keywords
- Cells, Cultured
- Cornea/cytology
- Diglycerides/immunology
- Epithelium, Corneal/immunology
- Flagellin/immunology
- Gene Expression/drug effects
- Gene Expression Profiling
- Humans
- I-kappa B Kinase/genetics
- Immunity, Innate
- Interleukin-33
- Interleukins/genetics
- Lipopolysaccharides/immunology
- NF-kappa B/metabolism
- Oligopeptides/immunology
- Poly I-C/immunology
- Primary Cell Culture
- Quinolines/pharmacology
- Signal Transduction
- Toll-Like Receptors/agonists