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.
ABSTRACT The mechanism of action involved in how Dermatophagoides pteronyssinus (Der p) 1 initiates the nasal allergic cascade is poorly understood.
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.
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.
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.
- Chest 01/2001; 119(5):1329-1336. · 5.85 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Intranasal steroids have proved to be the most effective class of drugs in reducing the symptoms of allergic rhinitis. This clinical response reflects the broad anti-inflammatory activity that has been demonstrated for corticosteroids. Single doses of topical corticosteroids administered before nasal allergen challenge block the late-phase reaction, whereas repeated dosing with intranasal steroids blocks both the early and the late response, as well as the priming phenomenon. Nasal inflammation is accomplished through a number of effector cells and mechanisms, which in turn are produced by director cells through the release of cytokines and chemokines. The anti-inflammatory action of corticosteroids is largely effected through blocking the synthesis and release of these cytokines/chemokines.Journal of Allergy and Clinical Immunology 11/1999; 104(4 Pt 1):S138-43. · 12.05 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Proteolytic activity is a central biochemical property that endows molecules with intrinsic allergenicity. Thus, the cysteine protease of dust mite, Der p1, the aspartic protease of cockroach, Bla g 2, the serine protease of Aspergillus fumigatus and the bacterial subtilisins are all major allergenic molecules responsible for the increase in asthma and atopic conditions worldwide. These proteases induce Th2-driven inflammatory responses in the airways by disrupting the epithelial cell junctions so that these, and other molecules, gain access to, and alter the function of, underlying cells of the innate immune system (dendritic cells, mast cells, basophils and macrophages) and B and T cells. Helminth parasites secrete proteases to gain entry into their hosts, and to feed on and migrate through tissues. Their action leads to tissue damage and the activation of inflammatory responses dominated by elevated IgE, eosinophilia and Th2 cells, much like allergenic responses. In certain situations, such as in acute infections (especially with zoonotic helminths), proteases secreted by helminths may sensitise individuals to allergens. However, the anti-inflammatory responses observed in chronic helminthiases, involving IL-10 and TGFBeta, that are primarily responsible for controlling immune-mediated damage to the host that is initiated by secreted proteases, coincidentally protects against similar inflammatory damage by allergens.Chemical immunology and allergy 02/2006; 90:45-64.