| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2006: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2005: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000)
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| Research Abstract |
We analyzed whether cysteine protease activity of recombinant house dust mite major group 1 allergens (rDer p 1, rDer f 1) can modulate immune responses, cause tissue-barrier disruption, and activate cells. The allergens used were highly purified and retained allergenicity and enzymatic activity equivalent to natural ones (Takai et al., J Allergy Clin Immunol, 2005 ; BBRC, 2005). Results obtained are as follows.
1.IgE and IgG eliciting activity of rDer p 1 in mice was remarkably reduced by treatment with an irreversible cysteine protease inhibitor (Kikuchi et al., J Immunol, 2006).
2.Skin barrier function was reduced by the cysteine protease activity of rDer f 1 in mice (Nakamura et al., J Invest Dermatol, 2006).
3.rDer p 1 and rDer f 1 activated cultured human keratinocytes and cystatin A, which is an inhibitor constitutively expressed in the skin, blocked this (Kato et al., J Allergy Clin Immunol, 2005). SCCA-2, which is an inducible protease inhibitor expressed by human bronchial epithelial cells, can also inhibit the cysteine protease activity of rDer p 1 and rDer f 1 (Sakata et al., J Biol Chem, 2004; BBRC, 2004).
Taken together, the cysteine protease activity of the mite group 1 allergens is now considered involved in the sensitization process toward IgE production at least three ways, by reducing the tissue-barrier function, stimulating keratinocytes and mucosal epithelial cells, and by modulating immune responses. The human body has a defensive system by protease inhibitors against them. Defect in this defensive system caused by environmental or genetic factors might be a causative factor for initiation of sensitization toward allergic diseases.
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