EP4 receptor signalling in immature B cells involves cAMP and NF-κB dependent pathways
Autor: | Martina Gobec, Matevz Prijatelj, Teja Celhar, Irena Mlinarič-Raščan |
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Rok vydání: | 2012 |
Předmět: |
B-cell receptor
Interleukin 5 receptor alpha subunit EP4 Receptor Pharmaceutical Science Tropomyosin receptor kinase B Biology Dinoprostone Interleukin 10 receptor alpha subunit Cell Line Mice Growth factor receptor NF-KappaB Inhibitor alpha Cyclic AMP Animals Cell Proliferation Pharmacology Precursor Cells B-Lymphoid Colforsin NF-kappa B Molecular biology Cyclic AMP-Dependent Protein Kinases Interleukin 10 Immune System Diseases Interleukin-21 receptor Adenylyl Cyclase Inhibitors lipids (amino acids peptides and proteins) I-kappa B Proteins Receptors Prostaglandin E EP4 Subtype Signal Transduction |
Zdroj: | The Journal of pharmacy and pharmacology. 64(8) |
ISSN: | 2042-7158 |
Popis: | Objectives Delineation of EP4 receptor signalling properties in immature B cells. Methods WEHI 231 cells were used as a model of immature B lymphocytes. The effects of PGE2, EP4 receptor antagonist, EP4 receptor agonist, forskolin and adenylate cyclase inhibitor on proliferation of WEHI 231 cells were examined by MTS assay. Cyclic adenosine monophosphate (cAMP) levels were examined by ELISA, whereas phosphorylation of vasodilator-stimulated phosphoprotein (VASP), kinase, extracellular signal-regulated kinase1/2, IκB-α and nuclear factor (NF)-κB subunit p105 were subjected to Western blot analysis. Translocation of NF-κB subunit p65 and EPRAP (EP4 receptor associated protein) was examined by fluorescence microscopy. Levels of early growth response factor (Egr)-1 mRNA were determined by quantitative PCR. Key findings We identified the EP4 receptor as the principal molecule mediating the growth-suppressive effect of prostaglandin E2 in WEHI 231 cells. EP4 receptor activation results in cAMP formation and the activation of protein kinase A, NF-κB1 p105 subunit stabilization and inhibition of IκBα phosphorylation, followed by the accumulation of NF-κB p65 subunit in the cell cytoplasm, whereas the activation of PI3K is not involved in EP4 receptor signalling. Elevation of cAMP and inhibition of NF-κB activation are two possible mechanisms by which the EP4 receptor inhibits the proliferation of immature B lymphocytes. Conclusions Modulation of the EP4 receptor on immature B lymphocytes provides important insight into the observed action of PGE2 and opens new possibilities for the development of therapies for autoimmune diseases, leukaemia and lymphomas. |
Databáze: | OpenAIRE |
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