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.
Seto
Takahiko
T
Atopy (Allergy) Research Center, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, Japan.
Takai
Toshiro
T
Ebihara
Nobuyuki
N
Matsuoka
Hiroyuki
H
Wang
Xiao-Ling
XL
Ishii
Akira
A
Ogawa
Hideoki
H
Murakami
Akira
A
Okumura
Ko
K
D000818:Animals; D002457:Cell Extracts / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology; D003228:Conjunctiva / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000276:immunology; D040001:Dermatophagoides farinae / Q000201:enzymology / Q000276:immunology*; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology; D016209:Interleukin-8 / Q000037:antagonists & inhibitors / Q000276:immunology; D053481:Secretory Leukocyte Peptidase Inhibitor / Q000494:pharmacology* / Q000502:physiology; D012697:Serine Endopeptidases / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D000515:alpha 1-Antitrypsin / Q000494:pharmacology / Q000502:physiology; D000093242:Interleukin-6 Inhibitors
D002457:Cell Extracts; D016207:Cytokines; D015850:Interleukin-6; D016209:Interleukin-8; D053481:Secretory Leukocyte Peptidase Inhibitor; D012697:Serine Endopeptidases; D000515:alpha 1-Antitrypsin; D000093242:Interleukin-6 Inhibitors