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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.

Interaction of Der p 2 with Toll-like Receptor 4 and its Effect on Cytokine Secretion