DIKUL - logo
(UL)
  • EP4 receptor signalling in immature B cells involves cAMP and NF-kB dependent pathways
    Prijatelj, Matevž ...
    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, IkB-aand nuclear factor (NF)-kB subunit p105 were subjected to Western blot analysis. Translocation of NF-kB subunit p65 and EPRAP (EP4 receptor associated protein) was examined by fluorescence microscopy. Levels of early growth response factor (Egr)-1mRNA 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-kB1 p105 subunit stabilization and inhibition of IkBa phosphorylation, followed by the accumulation of NF-kB p65 subunit in the cellcytoplasm, whereas the activation of PI3K is not involved in EP4 receptor signalling. Elevation of cAMP and inhibition of NF-kB 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.
    Source: Journal of Pharmacy and Pharmacology. - ISSN 0022-3573 (Vol. 64, iss. 8, 2012, str. 1090-1098)
    Type of material - article, component part
    Publish date - 2012
    Language - english
    COBISS.SI-ID - 3274097

    Link(s):

    http://onlinelibrary.wiley.com/doi/10.1111/j.2042-7158.2012.01499.x/pdf
    http://onlinelibrary.wiley.com/doi/10.1111/j.2042-7158.2012.01499.x/abstract;jsessionid=BFA3BB6972E6E5457443574F9C112A69.d01t01
    DOI

source: Journal of Pharmacy and Pharmacology. - ISSN 0022-3573 (Vol. 64, iss. 8, 2012, str. 1090-1098)

loading ...
loading ...
loading ...

Shelf entry