Inhibition of DC differentiation by PGE₂, proinflammatory cytokines, and TLR ligands is associated with the induction of endogenous COX2- and MDSC-associated suppressive factors. (A) Expression of COX2 mRNA (panel A left) and protein (panel A right) levels is induced by synthetic PGE₂, initiating a positive feedback loop in iMCs. Regulation of COX1 and COX2 expression by synthetic PGE₂ was analyzed after 6-10 hours. (B) Induction of immunosuppressive factors IL-10, NOS2, IDO1, and IL-4Rα by synthetic PGE₂. (C-D) Induction of PGE₂ secretion (C) and COX2 mRNA (D left) and protein (D right) by the COX2 activators LPS (TLR4 ligand), IL-1β, and IFN-γ. (E) Celecoxib suppresses the induction of immunosuppressive factors (IDO1, IL-10, NOS2, and IL-4Rα) by COX2 activators. All data (panels A-E) were confirmed in at least 3 independent experiments. Histograms present data from a single representative experiment with different donors as mean ± SD. *P < .05; **P < .01; and ***P < .001.