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Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Luschnig-Schratl, P; Sturm, EM; Konya, V; Philipose, S; Marsche, G; Fröhlich, E; Samberger, C; Lang-Loidolt, D; Gattenlöhner, S; Lippe, IT; Peskar, BA; Schuligoi, R; Heinemann, A.
EP4 receptor stimulation down-regulates human eosinophil function.
Cell Mol Life Sci. 2011; 68(21): 3573-3587.
Doi: 10.1007/s00018-011-0642-5
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- Leading authors Med Uni Graz
- Heinemann Akos
- Luschnig Petra
- Co-authors Med Uni Graz
- Böhm Eva
- Fröhlich Eleonore
- Gattenlöhner Stefan
- Konya Viktoria
- Lang-Loidolt Doris
- Lippe Irmgard Theresia
- Marsche Gunther
- Meindl Claudia
- Peskar Bernhard
- Schuligoi Rufina
- Sonia Philipose Sonia Philipose
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- Abstract:
- Accumulation of eosinophils in tissue is a hallmark of allergic inflammation. Here we observed that a selective agonist of the PGE(2) receptor EP4, ONO AE1-329, potently attenuated the chemotaxis of human peripheral blood eosinophils, upregulation of the adhesion molecule CD11b and the production of reactive oxygen species. These effects were accompanied by the inhibition of cytoskeletal rearrangement and Ca(2+) mobilization. The involvement of the EP4 receptor was substantiated by a selective EP4 antagonist, which reversed the inhibitory effects of PGE(2) and the EP4 agonist. Selective kinase inhibitors revealed that the inhibitory effect of EP4 stimulation on eosinophil migration depended upon activation of PI 3-kinase and PKC, but not cAMP. Finally, we found that EP4 receptors are expressed by human eosinophils, and are also present on infiltrating leukocytes in inflamed human nasal mucosa. These data indicate that EP4 agonists might be a novel therapeutic option in eosinophilic diseases.
- Find related publications in this database (using NLM MeSH Indexing)
- Antigens, CD11b - metabolism
- Calcium - metabolism
- Calcium Channels - chemistry
- Cell Movement -
- Cyclopentanes - pharmacology
- Dinoprostone - pharmacology
- Down-Regulation -
- Eosinophils - drug effects
- Humans -
- Inflammation - metabolism
- Isoindoles - pharmacology
- Nasal Mucosa - metabolism
- Phosphatidylinositol 3-Kinases - metabolism
- Protein Kinase C - metabolism
- Protein Kinase Inhibitors - pharmacology
- Reactive Oxygen Species - metabolism
- Receptors, Prostaglandin E, EP4 Subtype - agonists
- Sulfonamides - pharmacology
- Thioglycolates - pharmacology
- Find related publications in this database (Keywords)
- Eosinophils
- Prostaglandins
- Receptors
- Chemotaxis
- Reactive oxygen species
- Degranulation