Proinflammatory Signalling Cascades
Model by Haegeman, Eur Respir J 2003
Under one model of inflammatory gene induction, a dual signalling pathway is proposed. On the one hand, the transcription factor NF-kB is released from its inhibitory molecule and is able to bind onto various inflammatory gene protmoers. On the other, the MAPK pathways are concomitantly activated and will lead to specific phosphorylation of the NF-kBp65 subunit by MSK1 at a crucial amino acid residue, which is essential for enhanceosome building, while MSK1, haivng been recruited at inflammatory promoter regions, also phosphorylates the surrounding chromatin tails, contributing to local chromatin relaxation and facilitating gene transcription.
Model showing gene repression by glucocorticoids. By Haegeman, Eur Respir J 2003
Glucocorticoids bind to the glucocorticoid receptor (GR), which trnaslocates into the nucleus and inhibits inflammatory gene expression by specifically interacting with the activating interface between NF-kBp65 and the basal trnascription machinery (BTM), thus inhibiting gene expression in a promoter specific way.
