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- Title
House dust mite‐derived serine protease upregulates gene expression of interleukin‐33 in canine keratinocytes via protease‐activated receptor‐2.
- Authors
Nishimura, Rinka; Miyajima, Masaki; Takahashi, Kaho; Hirokawa, Marin; Hara, Yuna; Kimura, Junpei; Ohmori, Keitaro
- Abstract
Background: The involvement of interleukin (IL)‐33 produced by keratinocytes has been suggested in the pathogenesis of canine atopic dermatitis (cAD). House dust mite (HDM)‐derived proteases induce the production of various cytokines and chemokines in keratinocytes via protease‐activated receptor‐2 (PAR‐2); however, their effects on IL‐33 mRNA expression in canine keratinocytes have not been determined. Hypothesis/Objective: To clarify whether HDM‐derived proteases induce IL‐33 mRNA expression in canine keratinocytes via PAR‐2. Methods and materials: Expression of IL‐33 mRNA was quantified by real‐time PCR in a cell line of canine progenitor epidermal keratinocytes (CPEK) stimulated with Dermatophagoides farinae (Der f) whole body extract, Der f pre‐treated with cysteine protease and serine protease inhibitors, and trypsin. Trypsin and Der f‐mediated IL‐33 mRNA expression also was measured in CPEK cells treated with a PAR‐2 antagonist. Results: Der f enhanced IL‐33 mRNA expression in CPEK cells in incubation time‐ and dose‐dependent manners. Der f pre‐treated with a serine protease inhibitor, and not a cysteine protease inhibitor, abrogated an increase in IL‐33 mRNA expression in CPEK cells. Trypsin also enhanced IL‐33 mRNA expression in CPEK cells. Trypsin‐mediated IL‐33 mRNA expression was completely abolished by a PAR‐2 antagonist, while Der f‐mediated IL‐33 mRNA expression was partially and significantly diminished by it. Conclusions and clinical relevance: Der f‐derived serine protease upregulated IL‐33 mRNA expression in CPEK cells at least in part via PAR‐2. These findings suggest that HDM may be involved in the development of CAD by increasing IL‐33 mRNA expression in keratinocytes.
- Subjects
KERATINOCYTES; INTERLEUKIN-33; CYSTEINE proteinase inhibitors; HOUSE dust mites; GENE expression; TRYPSIN; PROTEOLYTIC enzymes; ELASTASES
- Publication
Veterinary Dermatology, 2022, Vol 33, Issue 1, p72
- ISSN
0959-4493
- Publication type
Article
- DOI
10.1111/vde.13023