Regulation of Constitutive Neutrophil Apoptosis Due to House Dust Mite Allergen in Normal and Allergic Rhinitis Subjects

Abstract

House dust mite (HDM) is a primary allergen in allergic rhinitis (AR) and asthma. Neutrophil apoptosis is associated with allergic diseases and innate immunity to infection. The present study examined how HDM affects constitutive neutrophil apoptosis in normal and AR subjects. Total IgE increased in AR subjects when compared to normal subjects, and patients with AR were HDM-specific IgE positive (+), which is specific IgE to Dermatophagoides pteronissinus and Dermatophagoides farinae. In normal and AR subjects, neutrophil apoptosis was inhibited by extract of Dermatophagoides pteronissinus (DP), but not by extract of Dermatophagoides farina (DF). Aprotinin (serine protease inhibitor) and E64 (cysteine protease inhibitor) have no effect on neutrophil apoptosis due to DP. The anti-apoptotic effect of DP was blocked by TLR4i, an inhibitor of TLR4, rottlerin, an inhibitor of PKCδ, PD98059, an inhibitor of ERK, and BAY-11-7085, an inhibitor of NF-κB. DP induced PKCδ, ERK, and NF-κB activation in a time-dependent manner. DP inhibited the cleavage of procaspase 3 and procaspase 9. The expression of IL-6, IL-8, TNF-α, G-CSF, GM-CSF, and CCL2 increased in the supernatant collected from the normal and AR neutrophils after DP treatment and the supernatant inhibited the apoptosis of normal and AR neutrophils. In summary, DP has anti-apoptotic effects on neutrophils of normal and AR subjects through the TLR4/PKCδ/ERK/NF-κB pathway, and this finding may contribute to solution of the pathogenic mechanism of allergic diseases triggered by DP.

Individualized Treatment of Allergic Rhinitis According to Nasal Cytology

“…A peak in the number of neutrophils was found during the period of maximal HDM-allergic inflammation 14. It is reported that Der p has anti-apoptotic effects on neutrophils through the toll-like receptor 4 (TLR4)/protein kinase C (PKC)δ/extracellular signal-regulated kinase (ERK)/nuclear factor-kappa B (NF-κB) pathway, which may prolong the survival time of local neutrophils 17. In addition, interleukin (IL)-17 is increased in AR patients, which could recruit a large number of neutrophils 18.…”

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

“…Der p 2 is an essential allergen, which binds to serum IgE of allergy patients. We previously demonstrated that allergic disease is associated with regulation of neutrophil apoptosis and HDM, and that HDM inhibits the spontaneous apoptosis of neutrophils by cytokine secretion of lymphocytes via PAR2 [16,17]. In this study, we examined that Der p 2 regulates neutrophil apoptosis by inducing cytokine production in lymphocytes.…”

Different anti-apoptotic effects of house dust mite allergen on eosinophil apoptosis between atopic and non-atopic asthmatic subjects

“…The antiapop totic signal due to DP is associated with activation of TLR4, PI3K, Akt, ERK, and NF-κB (Figure 4). The HDM mediated antiapoptotic effect through TLR4 in neutrophil apoptosis and PI3K, ERK, and NF-κB is as sociated with eosinophil apoptosis 18,26 . DP also medi ates the antiapoptotic signal by inhibiting the cleavage of procaspase 3 and procaspase 9 ( Figure 5).…”

“…Production of HDM IgE after exposure to HDM is consistently related to asthma development and exacerbation, and therefore used in the diagnosis, treatment and management of asthma 4,16,17 . We recently identified an antiapoptotic effect of DP on neutrophil apoptosis in allergic diseases 18 . Based on these findings, we investigated whether HDM is involved in pathoge nesis and exacerbation of asthma by inhibiting eosino phil apoptosis.…”