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House dust mite allergen suppresses neutrophil apoptosis by cytokine release via PAR2 in normal and allergic lymphocytes

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Abstract

House dust mite (HDM) is an essential allergen in allergic diseases such as allergic rhinitis and asthma. The pathogenic mechanism of allergy is associated with cytokine release of lymphocytes and constitutive apoptosis of neutrophils. In this study, we examined whether HDM induces cytokine release of lymphocytes and whether the secretion of cytokines is involved in modulation of neutrophil apoptosis. In normal and allergic subjects, extract of Dermatophagoides pteronyssinus (DP) increased IL-6, IL-8, MCP-1, and GM-CSF secretion in a time-dependent manner. This secretion was suppressed by PAR2i, an inhibitor of PAR2, in a dose-dependent manner, as well as by LY294002, an inhibitor of PI3K, AKTi, an inhibitor of Akt, PD98059, an inhibitor of ERK, and BAY-11-7085, and an inhibitor of NF-κB. DP induced ERK and NF-κB activation in a time-dependent manner. ERK activation was suppressed by PAR2i, LY294002, and AKTi, and NF-κB activation was blocked by PAR2i, LY294002, AKTi, and PD98059. Supernatants collected from normal and allergic neutrophils after DP treatment inhibited the apoptosis of normal and allergic neutrophils through suppression of caspase 9 and caspase 3 cleavage. DP inhibited neutrophil apoptosis in coculture of normal neutrophils with normal lymphocytes, similar to the anti-apoptotic effects of DP on neutrophils alone. DP more strongly inhibited apoptosis of allergic neutrophils cocultured with allergic lymphocytes than allergic neutrophils without lymphocytes. In summary, DP induces the release of cytokines through the PAR2/PI3K/Akt/ERK/NF-κB pathway, which has anti-apoptotic effects on neutrophils of normal and allergic subjects. These results will facilitate elucidation of the pathogenic mechanism of allergic diseases.

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Acknowledgments

We thank normal volunteers and allergic patients to participate in this study.

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Authors and Affiliations

  1. Department of Biomedical Laboratory Science, School of Medicine, Eulji University, 77, Gyeryoung-ro 771 beon-gil, Jung-Gu, Daejeon, 34824, Republic of Korea

    Na Rae Lee & In Sik Kim

  2. BK21 Plus Program, Department of Senior Healthcare, Graduate School, Eulji University, Daejeon, 34824, Republic of Korea

    Seung Yeop Baek, Ayoung Gu, Da Hye Kim, Seong Yeol Kim & In Sik Kim

  3. Department of Clinical Laboratory Science, Wonkwang Health Science University, 501, Iksandaero, Iksan, 54538, Republic of Korea

    Ji-Sook Lee

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  1. Na Rae Lee
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Correspondence to Ji-Sook Lee or In Sik Kim.

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Lee, N.R., Baek, S.Y., Gu, A. et al. House dust mite allergen suppresses neutrophil apoptosis by cytokine release via PAR2 in normal and allergic lymphocytes. Immunol Res 64, 123–132 (2016). https://doi.org/10.1007/s12026-015-8730-5

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