FIGURE 6.

P2Y₁₁ receptor‐driven release of soluble TNF receptors depends on intracellular cAMP and on TACE/ADAM17: synergistic enhancement by IL‐1α and IL‐1ß (a) M2 macrophages were treated with ATPγS in the presence or absence of increasing concentrations of the phosphodiesterase (PDE) inhibitors IBMX (nonselective) or rolipram (PDE4‐selective). The antagonist NF340 was used to confirm that agonist‐mediated responses were specific to stimulation of P2Y₁₁ receptors. sTNFR2 was measured in cell culture supernatants. (b) M2 macrophages were treated with ATPγS in the presence or absence of increasing concentrations of the TACE/ADAM17 inhibitors TAPI‐1 and TAPI‐2. The antagonist NF340 was used to confirm that agonist‐mediated responses were specific to stimulation of P2Y₁₁ receptors. sTNFR2 was measured in cell culture supernatants. (c) M2 macrophages were treated for 24 h with increasing doses of IL‐1α or IL‐1ß either alone or in combination with the P2Y₁₁ receptor agonist ATPγS (10 μM). The antagonist NF340 (10 μM) was used to confirm that agonist‐mediated responses were specific to stimulation of P2Y₁₁ receptors. For all graphs, data shown are means ± SEM from five independent donors. *P ≤ .05, significantly different as indicated; one‐way ANOVA