IKKβ regulates endothelial thrombomodulin in a Klf2-dependent manner.

ABSTRACT:

Background

Endothelial thrombomodulin (TM) is critically involved in anticoagulation, anti-inflammation, cytoprotection and normal fetal development. Tumor necrosis factor alpha (TNFα) suppresses TM expression.

Objective

TNFα has been shown to down-regulate TM partly via activation of nuclear factor kappa B (NF-κB). However, because the TM promoter lacks an NF-κB binding site, the direct involvement of NF-κB has been controversial. We investigated the role of the upstream regulatory serine kinase, inhibitory kappa-B kinase-β (IKKβ), in TM expression and function with or without TNFα treatment.

Methods

Inhibition of IKKβ was achieved by specific chemical inhibitors, siRNA or shRNA. TM expression was assessed by qRT-PCR, Western blot, flow cytometry, luciferase reporter

SUBMITTER: Pathak R 

PROVIDER: S-EPMC4163124 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature