The IκB kinase (IKK) complex acts as the gatekeeper of canonical NF-κB signaling, thereby regulating immunity, inflammation and cancer. It consists of the catalytic subunits IKKα and IKKβ and the regulatory subunit NEMO/IKKγ. Here, we show that the ubiquitin binding domain (UBAN) in NEMO is essential for IKK/NF-κB activation in response to TNFα, but not IL-1β stimulation. By screening a natural...

Glyceollins, produced to induce disease resistance responses against specific species, such as an incompatible pathogen Phytophthora sojae in soybeans, have the potential to exhibit anti-inflammatory activity in RAW 264.7 cells. To investigate the anti-inflammatory effects of elicited glyceollins via a signaling pathway, we studied the glyceollin signaling pathway using several assays including...

The NF-κB signalling pathway regulates many different biological processes from the cellular level to the whole organism. The majority of these functions are completely dependent on the activation of the cytoplasmic IKK kinase complex that leads to IκB degradation and results in the nuclear translocation of specific NF-κB dimers, which, in general, act as transcription factors. Although this is...

4'-Hydroxywogonin (4'-HW), a flavonoid, has been isolated from various plants and shown to inhibit NO production in macrophages. However, the molecular mechanisms and its in vivo activity have not been determined. Our study aimed to investigate the mechanisms underlying the anti-inflammatory effects of 4'-HW in vitro and in vivo. We showed that 4'-HW potently reduced the expression levels of CO...

NF-κB activation is a critical signaling event in the inflammatory response and has been implicated in a number of pathological lung diseases. To enable the assessment of NF-κB activity in the lungs, we transfected a luciferase based NF-κB reporter into the lungs of mice or into Raw264.7 cells in culture. The transfected mice showed specific luciferase expression in the pulmonary tissues. Using...

The activated NF-κB signaling pathway plays an important role in pathogenesis of primary Sjögren's syndrome (pSS). The inhibitor of κB (IκB) kinase (IKK) family such as IKKα, IKKβ, IKKγ, and IKKε, is required for this signaling. Our aim was to investigate the role of IKKα/β/γ/ε in patients with untreated pSS. In minor salivary glands from pSS patients, phosphorylated IKKε (pIKKε), pIκBα, and pN...

Monocyte-derived antigen presenting cells (APC) are central mediators of the innate and adaptive immune response in inflammatory diseases. As such, APC are appropriate targets for therapeutic intervention to ameliorate certain diseases. APC differentiation, activation and functions are regulated by the NF-κB family of transcription factors. Herein, we examined the effect of NF-κB inhibition, vi...

OBJECTIVE Nuclear factor kappa B (NF-κB) pathway and oxidative stress participate in endothelial dysfunction, which is one of the causes of pre-eclampsia. Among the human antioxidant mechanisms, there are the enzymes catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD). Our aim was to measure NF-κB, its inhibitor (IKK) and oxidative stress in placenta and umbilical cord o...

Background and objectives: Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) inhibition results in an increase in apoptosis. It has been demonstrated that NF-κB subunit p65 phosphorylation at the IκB kinase phosphorylation site serine 536 (Ser536) is essential for the NF-κB nuclear translocation and activation. Therefore, NF-κB can be downregulated by suppressing its phosph...

Recent work has indicated that platelets, which are anucleate blood cells, significantly contribute to inflammatory disorders. Importantly, platelets also likely contribute to various inflammatory secondary disorders that are increasingly associated with Human Immunodeficiency Virus Type-1 (HIV) infection including neurological impairments and cardiovascular complications. Indeed, HIV infection...