Figure 7.

Prostaglandin E₂ (PGE₂) inhibits CD25 expression on lymph node cells (LNCs) via the EP4 receptor and is produced by cardiosphere-derived cells (CDCs) in response to direct contact with LNCs and TNF-α. When LNCs are activated using ConA, CD25 has high staining intensity, which is significantly less when they are treated with PGE₂ (n = 3, p < 0.001, a). This effect is partially blocked by the addition of L-161982, a specific EP4 receptor antagonist (n = 3, p < 0.001, a). Additionally, when CDCs are cultured with stimulated LNCs, they produce high levels of PGE₂ compared to either cell type alone (n = 3, p < 0.001, b). PGE₂ production is ameliorated when CDCs are separated from LNCs by a transwell (n = 3, p < 0.001, b). Indomethacin completely prevents CDCs from producing PGE₂ (n = 3, p = 1.00, b). PGE₂ production could be induced in CDCs cultured with 50 ng mL⁻¹ TNF-alpha (n = 3, p < 0.05, c) but not with IFN-gamma (n = 3, p = 0.31, c). Bars represent mean ± SEM of 3 dogs.