The effects of IKK-beta inhibition on early NF-kappa-B activation and transcription of downstream genes.

ABSTRACT: Small molecule approaches targeting the nuclear factor kappa B (NF-kB) pathway, a regulator of inflammation, have thus far proven unsuccessful in the clinic in part due to the complex pleiotropic nature of this network. Downstream effects depend on multiple factors including stimulus-specific temporal patterns of NF-kB activity. Despite considerable advances, genome-level impact of changes in temporal NF-kB activity caused by inhibitors and their stimulus dependency remains unexplored. This study evaluates the effects of pathway inhibitors on early NF-?B activity and downstream gene transcription. 3T3 fibroblasts were treated with SC-514, an inhibitor targeted to the NF-kB pathway, prior to stimulation with interleukin 1 beta (IL-1?) or tumor necrosis factor alpha (TNF-?). Stimulus induced NF-?B activation was quantified using immunofluorescence imaging over 90-minutes and gene expression tracked over 6-hours using mRNA TagSeq. When stimulated with IL-1? or TNF-?, significant differences (P?

SUBMITTER: Bloom MJ 

PROVIDER: S-EPMC6348059 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature