Fig. 3
IL-1β upregulated Nav1.7 expression through the EP2-evoked PKA/CREB signaling pathway in TG explants. a Dose-course of phospho-CREB protein expression in TG after treatment with IL-1β (0.1 to 10 ng/mL) for 24 h. b Time-course of phospho-CREB protein expression in TG after treatment with IL-1β. c Upregulation of phospho-CREB protein expression by IL-1β in TG was blocked by COX-2 selective inhibitor NS398. d Upregulation of phospho-CREB protein expression by IL-1β in TG was blocked by EP2 selective antagonist PF-04418948. e PKA inhibitor H89 blocked IL-1β-induced upregulation of Nav1.7 and phospho-CREB protein expressions, but not COX-2 protein expression in TG. f PKA inhibitor H89 blocked IL-1β-induced upregulation of Nav1.7 mRNA expression, but not COX-2 mRNA expression in TG. g PKA inhibitor PKI-(6-22)-amide blocked IL-1β-induced upregulation of Nav1.7 and phospho-CREB protein expression, but not COX-2 protein expression in TG. h PKA inhibitor PKI-(6-22)-amide blocked IL-1β-induced upregulation of Nav1.7 mRNA expression, but not COX-2 mRNA expression in TG. i Forskolin upregulated Nav1.7 mRNA expression in TG for 24 h. j Adenylate cyclase agonist forskolin upregulated Nav1.7 and phospho-CREB protein expressions in TG for 24 h. k PKA inhibitor H89 blocked forskolin-induced upregulation of Nav1.7 and phospho-CREB protein expressions in TG. l PKA inhibitor PKI-(6-22)-amide blocked forskolin-induced upregulation of Nav1.7 and phospho-CREB protein expressions in TG. Quantification of protein expressions were presented as fold change of the control group (lower panel). One-way ANOVA or Independent samples t test, *P < 0.05 versus the control group, #P < 0.05 versus IL-1β group; n = 3. NS398: COX-2 selective inhibitor; PF-04418948: EP2 selective antagonist; H89 and PKI-(6-22)-amide: inhibitors of PKA; Forskolin: adenylate cyclase agonist