Schematic model for IL-1β-induced upregulation of Rgs4 expression in colonic smooth muscle cells via canonical IKK2/IκBα/NFκB signaling differentially modulated by MAPK pathways.

<p>IL-1β induces NFκB activation involving phosphorylation of IKK2, degradation of IκBα and nuclear translocation of p65/p50 leading to upregulation of <i>Rgs4</i> mRNA expression. IL-1β also activates three MAPKs. ERK1/2 and p38 MAPK enhance while JNK inhibits IL-1β-induced <i>Rgs4</i> upregulation. The effect of ERK1/2 is exerted on the canonical IKK2/IκBα/p65 pathway of NFκB activation and p38 MAPK may target at the chromatin level. The p38 may also inhibit JNK activity. Activation of the MEKK1-MKK4-JNK pathway down-regulates <i>Rgs4</i> expression through transcriptional repression at the chromatin level (via AP1 binding) and also signal inhibition of NFκB activation at the level of IKK2. The intricate interactions across various transcription factors and chromatin remodeling need further investigation. The solid arrows indicate the activation while the spotted arrows represent the inhibition.