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House dust mite allergen suppresses neutrophil apoptosis by cytokine release via PAR2 in normal and allergic lymphocytes
- Source :
- Immunologic research. 64(1)
- Publication Year :
- 2015
-
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.
- Subjects :
- 0301 basic medicine
MAPK/ERK pathway
Adult
Male
Allergy
Adolescent
MAP Kinase Signaling System
Neutrophils
medicine.medical_treatment
Dermatophagoides pteronyssinus
Immunology
Caspase 3
Apoptosis
03 medical and health sciences
chemistry.chemical_compound
Young Adult
medicine
Hypersensitivity
Animals
Humans
Receptor, PAR-2
LY294002
Antigens, Dermatophagoides
Lymphocytes
Enzyme Inhibitors
Child
PI3K/AKT/mTOR pathway
Cells, Cultured
Aged
House dust mite
Aged, 80 and over
Immunosuppression Therapy
biology
Middle Aged
biology.organism_classification
medicine.disease
030104 developmental biology
Cytokine
chemistry
Child, Preschool
Cytokines
Female
Subjects
Details
- ISSN :
- 15590755
- Volume :
- 64
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Immunologic research
- Accession number :
- edsair.doi.dedup.....b9d69f519cdca1c5531c613cca5599b7