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.
Highlights
Rhinitis is classified as allergic or non-allergic based on allergen sensitization [1,2]
Exposure of House dust mite (HDM) is closely associated with Allergic rhinitis (AR) Prior to evaluating the effects of HDM in neutrophil apoptosis of normal and AR subjects, we investigated the association of HDM with AR
The number of leukocytes including neutrophils and eosinophils in AR subjects was not different from that in normal subjects (Figure 1C). These results indicate that exposure to HDM is an important cause of AR pathogenesis
Summary
Rhinitis is classified as allergic or non-allergic based on allergen sensitization [1,2]. Allergic rhinitis (AR) is characterized by rhinorrhea, stuffy nose due to nasal obstruction, sneezing and itching, and its symptoms are caused by an immunological mechanism after exposure to allergen. AR is deeply related to other atopic diseases such as asthma. House dust mite (HDM), which includes two main species, Dermatophagoides pteronissinus and Dermatophagoides farinae, plays an important role in the onset and aggravation of allergic diseases, including AR [3,4,5]. Total IgE in the serum of AR subjects is high relative to normal subjects and HDM-specific IgE (HDM IgE) appears in AR patients. A recent study demonstrated the importance of immune dysregulation by HDM in AR [6]
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