کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1983648 1539926 2011 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
TLR-mediated induction of pro-allergic cytokine IL-33 in ocular mucosal epithelium
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
TLR-mediated induction of pro-allergic cytokine IL-33 in ocular mucosal epithelium
چکیده انگلیسی

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.


► We identify a TLR-dependent induction of IL-33 by microbial products.
► We explore a mechanism involved in IL-33 secretion and activation.
► We reveal TLR/NF-κB mediated signaling pathway for IL-33 induction.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The International Journal of Biochemistry & Cell Biology - Volume 43, Issue 9, September 2011, Pages 1383–1391
نویسندگان
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