SLPI prevents cytokine release in mite protease-exposed conjunctival epithelial cells.

House dust mites are a major source of allergens associated with allergic diseases including allergic conjunctivitis. Here, we demonstrate that mite-derived serine protease activity induces the release of cytokines from human ocular conjunctival epithelial cells in vitro and innate antiproteases, secretory leukocyte protease inhibitor (SLPI) and alpha1-antitrypsin, can inhibit the response. An extract prepared from a whole-mite culture induced the release of IL-6 and IL-8 and upregulated their gene expression in the human conjunctival epithelial cell line Chang, responses which were inhibited not only by a synthetic serine protease-specific inhibitor, AEBSF, but also by SLPI and alpha1-antitrypsin at a physiologically relevant concentration. The findings suggest a homeostatic role for SLPI and alpha1-antitrypsin against the proteases contained in allergen sources in the ocular conjunctiva and that exposure to house dust particles containing mite-derived serine protease activity could be involved in the initiation of sensitization through the ocular conjunctival epithelium and/or exacerbation of allergic conjunctivitis.