Fig. 7.

IL-1β-induced upregulation of RGS4 expression in colonic SMCs via canonical IKK2/IκB-α/NF-κB signaling is differentially modulated by the MAPK and PI3K/Akt/GSK3β pathways. IL-1β induces NF-κB activation involving the phosphorylation of IKK2, degradation of IκB-α, and nuclear translocation of p65/p50, leading to the upregulation of RGS4 mRNA expression. IL-1β also activates MAPK and PI3K. ERK1/2 and p38 MAPK enhance, whereas PI3K inhibits, IL-1β-induced RGS4 upregulation. The effect of ERK1/2 is exerted on the canonical IKK2/IκBα/p65 pathway of NF-κB activation, and p38 MAPK may target at the chromatin level. PI3K attenuates NF-κB activation at the level of IKK2 by inactivating GSK3β by increasing the phosphorylation of GSK3β via Akt.