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

Biochem Biophys Res Commun. 2009 Feb 13;379(3):681-5. doi: 10.1016/j.bbrc.2008.12.060. Epub 2008 Dec 25.

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.

MeSH terms

  • Animals
  • Cell Extracts / chemistry
  • Cell Extracts / immunology
  • Cell Extracts / pharmacology
  • Conjunctiva / cytology
  • Conjunctiva / drug effects*
  • Conjunctiva / immunology
  • Cytokines / antagonists & inhibitors*
  • Cytokines / immunology
  • Dermatophagoides farinae / enzymology
  • Dermatophagoides farinae / immunology*
  • Epithelial Cells / drug effects
  • Epithelial Cells / immunology
  • Humans
  • Interleukin-6 / antagonists & inhibitors
  • Interleukin-6 / immunology
  • Interleukin-8 / antagonists & inhibitors
  • Interleukin-8 / immunology
  • Secretory Leukocyte Peptidase Inhibitor / pharmacology*
  • Secretory Leukocyte Peptidase Inhibitor / physiology
  • Serine Endopeptidases / chemistry
  • Serine Endopeptidases / immunology*
  • Serine Endopeptidases / pharmacology
  • alpha 1-Antitrypsin / pharmacology
  • alpha 1-Antitrypsin / physiology

Substances

  • Cell Extracts
  • Cytokines
  • Interleukin-6
  • Interleukin-8
  • Secretory Leukocyte Peptidase Inhibitor
  • alpha 1-Antitrypsin
  • Serine Endopeptidases