dc.contributor.author | Gomi, Kaede. | en_US |
dc.date.accessioned | 2014-10-21T12:33:47Z | |
dc.date.available | 2002 | |
dc.date.issued | 2002 | en_US |
dc.identifier.other | AAINQ67649 | en_US |
dc.identifier.uri | http://hdl.handle.net/10222/55823 | |
dc.description | Prostaglandin E2 (PGE2) is overproduced in chronic inflammatory disorders, and acts on virtually every cell of the immune system. Although mast cells are implicated in the pathogenesis of inflammatory disorders, surprisingly little is known of the effects of PGE2 on mast cells. | en_US |
dc.description | We investigated the effects of PGE2 on mast cell degranulation and production of cytokines relevant to allergic disease. Mouse bone marrow-derived mast cells (BMMC) were treated with PGE2 alone or in the context of IgE-mediated activation. PGE2 treatment alone specifically enhanced interleukin (IL)-6 production, yet failed to modulate the production of a number of other mast cell cytokines. However in the context of IgE-mediated activation, PGE2 potentiated mast cell degranulation and selectively enhanced the production of IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumour necrosis factor-alpha (TNF-alpha). PGE 2 generally inhibits TNF-alpha production by many cell types through the elevation of intracellular cAMP. cAMP-elevating agents, forskolin and pentoxifylline, failed to similarly enhance IgE-mediated TNF-alpha production, arguing against a role for cAMP. PGE2 acts by binding to one of four prostaglandin E receptor subtypes (EP1--EP4). RT-PCR analysis of resting MC/9 cells revealed the expression of EP1 , EP3, and EP4 prostaglandin E receptor subtypes, including a novel variant form of the mouse EP1 receptor. Pharmacological studies using EP subtype-selective agonists indicated that PGE2 differentially regulated mast cell IL-6 and TNF-alpha production through the activation of EP1 and/or EP3 receptors, with a possible role for intracellular calcium. | en_US |
dc.description | Taken together, our data indicate that PGE2 may profoundly alter the nature of mast cell responses at sites of allergic inflammation. Furthermore, we have shown that PGE2 acts through EP receptor subtypes not normally associated with the regulation of the immune responses, providing another glimpse into the complexity of the immunomodulatory effects of PGE 2. | en_US |
dc.description | Thesis (Ph.D.)--Dalhousie University (Canada), 2002. | en_US |
dc.language | eng | en_US |
dc.publisher | Dalhousie University | en_US |
dc.publisher | | en_US |
dc.subject | Biology, Molecular. | en_US |
dc.subject | Health Sciences, Immunology. | en_US |
dc.title | Modulation of mast cell responses by prostaglandin E(2). | en_US |
dc.type | text | en_US |
dc.contributor.degree | Ph.D. | en_US |