Suppressive Effect of Arazyme on Neutrophil Apoptosis in Normal and Allergic Subjects

Abstract

Arazyme is a metalloprotease secreted by Aranicola proteolyticus that was previously shown to suppress cytokine expression of keratinocytes and endothelial cells and inhibit histopathological features in an atopic dermatitis-like animal model. However, the regulatory effects of arazyme in other allergic diseases have yet to be elucidated. In this study, we investigated whether arazyme is effective against neutrophil apoptosis in allergic diseases such as allergic rhinitis and asthma. Arazyme inhibited neutrophil apoptosis of normal subjects in a dose-dependent manner. However, the antiapoptotic effect of arazyme was reversed by LY294002, an inhibitor of PI3K, AKTi, an inhibitor of Akt, PD98059, an inhibitor of MEK, and BAY-11-7085, an inhibitor of NF-κB. Arazyme induced activation of NF-κB via PI3K/Akt/ERK pathway. The anti-apoptotic effect of arazyme is associated with inhibition of cleavage of caspase 3 and caspase 9. Arazyme inhibited constitutive apoptosis of neutrophil in a dose-dependent manner in allergic subjects, and its mechanism was shown to be associated with PI3K/Akt/ERK/NF-κB. The results presented here improve our understanding of neutrophil apoptosis regulation and will facilitate development of drugs for treatment of allergic diseases.

Suppressive Effect of Der p 2 on Constitutive Neutrophil Apoptosis by Cytokine Secretion of Normal and Allergic Lymphocytes

“…HDMs include a variety of allergen proteins, which function as cysteine and serine proteases, MD-mimic molecule, alpha amylase, chitinase, and arginine kinase [2,3,11,15]. Der p 2 is an essential allergen, which binds to serum IgE of allergy patients.…”

“…Allergic diseases including allergic rhinitis, asthma, and allergic dermatitis are caused by environmental, genetic, and immunological elements [1][2][3][4]. House dust mites (HDMs), which primarily consist of Dermatophagoides pteronissinus and Dermatophagoides farinae, are related to allergy pathogenesis [1,[5][6][7].…”

Interaction of Der p 2 with Toll-like Receptor 4 and its Effect on Cytokine Secretion

“…Allergic diseases include allergic rhinitis, asthma, and allergic conjunctivitis, and their symptoms are associated with inflammatory response. House dust mite (HDM) is a main allergen triggering and alleviating allergic diseases (Gaffin and Phipatanakul, 2009;Kemp, 2009;Kim et al, 2014a;Kim et al, 2014b;Lee et al, 2014). Dermatophagoides pteronyssinus, an important HDM, includes a variety of allergen proteins (Thomas et al, 2010;Kim et al, 2013).…”