Moreover, WAY significantly down-regulated the activation of NF-κB (<i>P</i> < 0.001) and AP-1 (<i>P</i> < 0.01, <i>P</i> < 0.05) in ASM cells from asthmatics and nonasthmatics.
Inflammation in asthma is characterised by the increased expression of multiple inflammatory genes regulated by pro-inflammatory transcription factors, such as nuclear factor-kappaB and activator protein-1, which bind to and activate coactivator molecules that acetylate core histones and switch on gene transcription.
These mediators are downstream targets for the transcription factors activator protein-1 (AP-1) and nuclear factor-kappaB (NF-kappaB), which control the expression of most immunomodulatory genes and whose activity and expression are elevated in asthma.
Secondary steroid resistance in asthma may arise in response to the release of cytokines that activate AP-1 and other transcription factors that bind directly to GR.
There may be an abnormal activation of AP-1 in steroid-resistant asthma, and high concentrations of beta 2-agonists may induce a secondary resistance by an interaction between the transcription factor CREB and the glucocorticoid receptor.
To study this reduced DNA binding, we examined the ability of the nuclear translocated transcription factors activator protein 1 (AP-1), nuclear factor kappa B (NF-kappa B) and cyclic AMP response element-binding protein (CREB) to bind to their DNA-binding sites and to interact with GR in PBMC from patients with steroid-sensitive and steroid-resistant asthma.