@article {Ratcliffe986, author = {M. J. Ratcliffe and A. Walding and P. A. Shelton and A. Flaherty and I. G. Dougall}, title = {Activation of E-prostanoid4 and E-prostanoid2 receptors inhibits TNF-α release from human alveolar macrophages}, volume = {29}, number = {5}, pages = {986--994}, year = {2007}, doi = {10.1183/09031936.00131606}, publisher = {European Respiratory Society}, abstract = {Prostaglandin (PG)E2 has been shown to inhibit mediator release from human alveolar macrophages (AMs), but the prostanoid receptor(s) mediating this response have not yet been documented. To investigate this, the present authors conducted a range of pharmacological and expression-based studies in monocyte-derived macrophages (MDMs) and AMs. MDMs were obtained by in vitro differentiation of monocytes from the peripheral blood of healthy human volunteers. Human AMs were obtained by perfusion of lung tissue from carcinoma resection patients. In MDMs, PGE2 potently inhibited lipopolysaccharide-induced tumour necrosis factor (TNF)-α release (p[A]50 8.51{\textpm}0.11, maximum inhibition 95.9{\textpm}4.8\%). In human AMs, PGE2 also inhibited TNF-α release but the observed concentration{\textendash}effect curve was very flat and inhibition was incomplete. The shape of the PGE2 curve in AMs suggested that its effects were mediated by activation of a heterogeneous receptor population. Expression studies combined with the use of various E-prostanoid (EP) receptor agonists and a selective EP4-receptor antagonist (Ono-AE2-227) confirmed that the inhibitory effects of PGE2 in both AMs and MDMs were mediated by activation of EP4 and EP2 receptors. These data indicate that both E-prostanoid4 and E-prostanoid2 selective agonists may have anti-inflammatory properties in lung diseases where macrophages play a role.}, issn = {0903-1936}, URL = {https://erj.ersjournals.com/content/29/5/986}, eprint = {https://erj.ersjournals.com/content/29/5/986.full.pdf}, journal = {European Respiratory Journal} }