Induction of IL-6 and IL-8 by house dust mite allergen Der p1 in cultured human nasal epithelial cells is associated with PAR/PI3K/NFkappaB signaling.
OBJECTIVE
The mechanism of action involved in how Dermatophagoides pteronyssinus (Der p) 1 initiates the nasal allergic cascade is poorly understood.


METHODS
We detected proinflammatory cytokine production (GM-CSF, TNF-α, IL-1β, IL-6, and IL-8) and associated signal molecules in primarily cultured nasal epithelial cells (NECs) from patients with allergic rhinitis (AR) after Der p1 stimulation, using ELISA, RT-PCR, and Western blot. We also evaluated the importance of protease-activated receptors (PAR)/phosphatidylinositol 3 kinase (PI3K)/NFκB signaling pathways in IL-6 and IL-8 production using glucocorticoids and specific inhibitors, LY294002 and PDTC.


RESULTS
We observed significantly elevated IL-6 and IL-8 production (both gene and protein) in NECs after Der p1 stimulation, and demonstrated that the expressions of PAR2, pAkt, and pp65 were upregulated after Der p1 stimulation, which were associated with IL-6 and IL-8 production in NECs.


CONCLUSIONS
These findings demonstrate that the PAR/PI3K/NFκB signaling pathway is involved in the induction of IL-6 and IL-8 in Der-p1-stimulated NECs from AR patients, and may have potential implications for the prevention and treatment of AR and asthma.
Shi
Jianbo
J
Otorhinolaryngology Institute of Sun Yat-Sen University, Guangzhou, China.
Luo
Qing
Q
Chen
Fenghong
F
Chen
Dehua
D
Xu
Geng
G
Li
Huabin
H
D000328:Adult; D039741:Antigens, Dermatophagoides / Q000276:immunology*; D060829:Arthropod Proteins; D001249:Asthma / Q000276:immunology; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D009297:Nasal Mucosa / Q000166:cytology / Q000276:immunology; D019869:Phosphatidylinositol 3-Kinases / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D044463:Receptor, PAR-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D044464:Receptor, PAR-2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012221:Rhinitis, Allergic, Perennial / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D055815:Young Adult
D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D012333:RNA, Messenger; D044463:Receptor, PAR-1; D044464:Receptor, PAR-2; D019869:Phosphatidylinositol 3-Kinases; D003546:Cysteine Endopeptidases; C451162:Dermatophagoides pteronyssinus antigen p 1