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KMID : 0603820150210030152
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Journal of Experimental & Biomedical Science
2015 Volume.21 No. 3 p.152 ~ p.159
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Interaction of Der p 2 with Toll-like Receptor 4 and its Effect on Cytokine Secretion
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Park Beom-Seok
Lee Na-Rae
Kim Mun-Jeong
Kim Seong-Yeol
Kim In-Sik
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Abstract
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Der p 2, which is a major allergen of house dust mite, plays an important role in the pathogenesis of allergic disease. There is controversy regarding whether Der p 2 binds to Toll-like receptor 4 (TLR4), and its inflammatory effect has not yet been elucidated. In the current study, we examined the interaction of Der p 2 with TLR4 and the effect of Der p 2 on cytokine release in THP-1 cells and lymphocytes. Among house dust mite extracts, recombinant TLR4 protein interacted with Der p 2. The overall structure of Der p 2 is characteristic of the immunoglobulin superfamily and contains ten β-strands, forming a β-cup fold with two anti-parallel β-sheets, and a short 310 helix. The two sheets can be separated, further allowing the formation of a large internal pocket, which is narrow and suitable for binding large flat molecules such as lipid-like molecules. Der p 2 caused increased secretion of IL-6, IL-8, and MCP-1, which are neutrophil survival factors, in human monocytic THP-1 cells in a time-dependent manner. Der p 2 also induces the release of cytokines in normal and allergic lymphocytes. Supernatant after treatment with Der p 2 inhibited neutrophil apoptosis. In coculture of lymphocytes with neutrophils, Der p 2 inhibited spontaneous apoptosis of allergic neutrophils. In summary, Der p 2 binds to TLR4 and induces an inflammatory response such as cytokine secretion in immune cells. These findings may enable elucidation of allergy pathogenesis by specific allergen of house dust mite.
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KEYWORD
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House dust mite, Der p 2, TLR4, Cytokine
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