Apremilast inhibited PDE4 expression, activated PKA–CREB and Epac‐Rap1 signalling, and subsequently interfered with JAK–STAT–SOCS3, PI3K–mTOR, NF‐κB, and MAPK pathways. (a) The mRNA expression of the isoforms of PDE4 in colonic tissue. (b) The expression of the isoforms of PDE4 and PKA–CREB signalling‐associated proteins. (c) Immunohistochemical staining for PDE4D, p‐p65, and p‐REK of colonic tissue. (d) Immunofluorescent staining for Epac1 in colonic tissue. Western blot analysis of JAK–STAT–SOCS3 signalling (e), NF‐κB‐ and MAPK‐mediated signalling (f) and PI3K–mTOR signalling (g). Data shown are representative images from western blot assays and from immunohistochemical staining. The summary data are shown as means ± SEM; n = 8 per group. *P < 0.05, significantly different from vehicle (DSS only) group