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SLPI prevents cytokine release in mite protease-exposed conjunctival epithelial cells
Takahiko Seto1, Toshiro Takai, Nobuyuki Ebihara
1Atopy (Allergy) Research Center, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, Japan.
Abstract:
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.
Insights
House dust mite serine proteases trigger allergic conjunctivitis by stimulating ocular cells. Innate antiproteases, secretory leukocyte protease inhibitor (SLPI) and alpha1-antitrypsin, can block this mite-induced inflammation.
Area of Science:
- Immunology
- Ophthalmology
- Allergology
Background:
- House dust mites are significant allergens linked to allergic diseases like allergic conjunctivitis.
- Mite-derived serine proteases are implicated in allergic responses.
- The role of ocular innate antiproteases in mitigating mite-induced inflammation is not fully understood.
Purpose of the Study:
- To investigate the effect of mite-derived serine protease activity on human conjunctival epithelial cells.
- To determine the inhibitory potential of innate antiproteases, secretory leukocyte protease inhibitor (SLPI) and alpha1-antitrypsin, against mite protease-induced responses.
- To explore the implications for allergic conjunctivitis pathogenesis.
Main Methods:
- Cultured human conjunctival epithelial cells (Chang cell line) were stimulated with a whole-mite extract.
- Cytokine release (IL-6, IL-8) and gene expression were measured.
- The effects of a synthetic serine protease inhibitor (AEBSF), SLPI, and alpha1-antitrypsin were assessed.
Main Results:
- Mite extract induced significant release and gene expression of IL-6 and IL-8 in conjunctival cells.
- These responses were effectively inhibited by AEBSF, SLPI, and alpha1-antitrypsin at physiological concentrations.
- SLPI and alpha1-antitrypsin demonstrated potent inhibition of mite protease activity.
Conclusions:
- Mite-derived serine proteases activate ocular conjunctival epithelial cells, contributing to allergic conjunctivitis.
- Innate antiproteases SLPI and alpha1-antitrypsin play a crucial homeostatic role by neutralizing mite proteases in the ocular environment.
- These findings suggest that mite protease activity in house dust may initiate sensitization or exacerbate allergic conjunctivitis via the ocular conjunctival epithelium.