PGE₂ enhances IGE mediated GM-CSF production by murine mast cells

Allergic inflammation is characterized by elevated numbers of eosinophils and other inflammatory cells in affected tissues, a phenomenon orchestrated, in part, by increased local levels of GM-CSF. We investigated the regulation of mast cell GM-CSF production by PGE₂ a prostanoid known to be induced at sites of inflammation. Murine bone marrow derived-mast cells (mBMMC) were stimulated with PGE₂ (10^-6-10^-12M) in the presence and absence of lipopolysaccharide (LPS) and supernatants were assayed for cytokine content by ELISA after 24 h. Parallel experiments were performed to assess PGE₂ effects in the context of IgE mediated mast cell activation using anti-dinitrophenyl (DNP) IgE-sensitized mBMMC stimulated concurrently with PGE₂ and DNP-human serum albumin (10ng/ml). PGE₂ treatment alone did not upregulate GM-CSF synthesis but did induce a significant increase in IL-6 production. IgE mediated activation of mBMMC induced significant production of GM-CSF over media controls (means 22.9 +/- 4.2 pg/ml and 0.64 +/- 0.30 pg/ml respectively; n=14) and PGE₂ (10^-6M) acted synergistically to more than double IgE- mediated GM-CSF production (50.1 +/- 8.4 pg/ml, n=10). Co-stimulation of mBMMC with LPS (5ug/ml) and PGE₂ (10^-6M) also slightly enhanced GM-CSF production (5.7 +/- 0.6 pg/ml; n=7) over that induced by LPS alone (4.2 +/- 0.4 pg/ml; n=7). These data demonstrate that PGE₂ induces activated mast cells to secrete increased amounts of GM-CSF and suggest that ongoing PGE₂ stimulation at sites of allergic inflammation may augment local chronic inflammatory processes.