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Mite serine protease activates protease-activated receptor-2 and induces cytokine release in human keratinocytes

T Kato1, T Takai, T Fujimura

  • 1Atopy Research Center, Juntendo University School of Medicine, Tokyo, Japan.

Allergy
|May 7, 2009
PubMed
Abstract

Insights

House dust mite serine proteases activate human keratinocytes, potentially contributing to atopic dermatitis. Cysteine proteases from Der f 1 and Der p 1 activate via a different pathway.

Area of Science:

  • Immunology
  • Dermatology
  • Biochemistry

Background:

  • House dust mites (HDM) produce serine and cysteine proteases.
  • Mite proteases are implicated in allergy pathogenesis.
  • The role of HDM serine proteases in keratinocyte activation was unknown.

Purpose of the Study:

  • To investigate the activation of human keratinocytes by HDM serine proteases.
  • To compare the effects of serine protease-rich extract with recombinant cysteine proteases (rDer f 1, rDer p 1).

Main Methods:

  • Incubation of primary human keratinocytes with whole mite culture extract (WCE) and recombinant allergens.
  • Measurement of cytokine release (IL-8, GM-CSF) and mRNA expression.
  • Assessment of intracellular calcium (Ca2+) mobilization.
  • Investigation of protease-activated receptor 2 (PAR-2) activation.

Main Results:

  • WCE and recombinant allergens induced IL-8 and GM-CSF release.
  • WCE significantly upregulated cytokine mRNA; rDer f 1 had minimal effect.
  • WCE stimulated Ca2+ mobilization, unlike rDer f 1 and rDer p 1.
  • WCE inhibited PAR-2 agonist-induced Ca2+ mobilization; rDer f 1 showed inefficient PAR-2 peptide cleavage.

Conclusions:

  • HDM serine protease activity activates keratinocytes, likely via PAR-2, contributing to atopic dermatitis.
  • Cysteine protease activity of Der f 1 and Der p 1 activates keratinocytes through an alternative mechanism.

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