NF-kappaB Signaling in Chronic Inflammatory Airway Disease

Abstract

Asthma and chronic obstructive pulmonary disease (COPD) are obstructive airway disorders which differ in their underlying causes and phenotypes but overlap in patterns of pharmacological treatments. In both asthma and COPD, oxidative stress contributes to airway inflammation by inducing inflammatory gene expression. The redox-sensitive transcription factor, nuclear factor (NF)-kappaB (NF-κB), is an important participant in a broad spectrum of inflammatory networks that regulate cytokine activity in airway pathology. The anti-inflammatory actions of glucocorticoids (GCs), a mainstay treatment for asthma, involve inhibition of NF-κB induced gene transcription. Ligand bound GC receptors (GRs) bind NF-κB to suppress the transcription of NF-κB responsive genes (i.e., transrepression). However, in severe asthma and COPD, the transrepression of NF-κB by GCs is negated as a consequence of post-translational changes to GR and histones involved in chromatin remodeling. Therapeutics which target NF-κB activation, including inhibitors of IκB kinases (IKKs) are potential treatments for asthma and COPD. Furthermore, reversing GR/histone acetylation shows promise as a strategy to treat steroid refractory airway disease by augmenting NF-κB transrepression. This review examines NF-κB signaling in airway inflammation and its potential as target for treatment of asthma and COPD.

Myricetin Attenuates LPS-induced Inflammation in RAW 264.7 Macrophages and Mouse Models

“…Previous studies demonstrated that LPS activated inflammatory signaling pathway nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) (Hayden and Ghosh, 2008;Schuliga, 2015). Accumulating evidence supports that the activation of the above two signaling pathway in lung tissue is up-regulated in mice processed LPS-induced ALI (Lv et al, 2017;Wu et al, 2016), while inhibitors of these signaling pathway not only suppressed the influx of neutrophils but also alleviated lung edema (Everhart et al, 2006;Lin et al, 2015;Santos et al, 2018).…”

Wogonoside alleviates inflammation induced by traumatic spinal cord injury by suppressing NF-κB and NLRP3 inflammasome activation

“…IκB is regulated by IκB kinase, which catalyzes phosphorylation of the 42' serine residue in IκB as a signal for degradation, which induces rapid degradation of IκB (typically within several min) and exposes the nuclear localization sequence of NF-κB (21). The nuclear localization sequence of NF-κB is disclosed and NF-κB is activated and translocated to nucleus (22). Once there, NF-κB binds with the κB locus in the NF-κB reactive gene to regulate gene transcription and downstream cellular processes, including cell growth, differentiation, adhesion, apoptosis and the inflammatory response (22).…”

“…The nuclear localization sequence of NF-κB is disclosed and NF-κB is activated and translocated to nucleus (22). Once there, NF-κB binds with the κB locus in the NF-κB reactive gene to regulate gene transcription and downstream cellular processes, including cell growth, differentiation, adhesion, apoptosis and the inflammatory response (22). Excessive phosphorylation of IκB results in a loss of NF-κB inhibition (23).…”

Anti-inflammatory properties of chloroform extracts from GW10-45, a new cultivar derived from Pleurotus ferulae, in RAW264.7 murine macrophages

“…세 포 외부에서 LPS와 같은 자극이 주어지면 세포 내로 신 호가 전달되어 NF-κB의 억제 단백질인 IκB (inhibitor of NF-κB)α의 인산화가 일어나고 인산화된 IκBα는 분해되 어 NF-κB의 인산화가 일어난다. 이후 인산화된 NF-κB 는 핵 내로 이동하여 iNOS와 COX-2 같은 NF-κB에 관 련된 gene들의 전사를 진행하게 된다 (Kim et al, 2011;Li and Verma, 2002;Schuliga, 2015;Barnes and Karin, 1997). 이러한 NF-κB와 IκBα의 인산화를 확인하기 위해 RAW264.7 세포에 CG45 (100 μg/ml)를 처리하고 LPS로 24시간 자극시킨 후 이들 단백질들의 발현에 대한 Western blot을 시행하였다.…”

“…일반적인 경우의 염증은 숙 주가 자신을 보호하는 매우 중요한 반응이지만, 지속적인 항원에 대한 노출이나 유전적 결함에 의해 염증반응이 지 속적이고 과도하게 일어날 경우, 만성적인 염증으로 진행 된다 (Jeong et al, 2014;Schuliga, 2015). 이러한 만성적 κ κ κ κ κ 염증은 조직에 치명적일 뿐만 아니라 류마티스 관절염, 치매, 암, 2형 당뇨 등의 질병을 일으키는 주요한 원인으 로 생각된다 (Libby, 2007;Kundu and Surh, 2008).…”