NFκB-dependent signaling is an important modulator of inflammation in several diseases including sepsis. G-protein-coupled receptor kinase-5 (GRK5) is an evolutionarily conserved regulator of the NFκB pathway. We hypothesized that GRK5 via NFκB regulation plays an important role in the pathogenesis of sepsis. To test this we utilized a clinically relevant polymicrobial sepsis model in mice that...

BACKGROUND Fn14 is a therapeutic target in various diseases. RESULTS Anti-Fn14 antibodies activate the alternative NFκB pathway but not other Fn14-related activities induced by soluble or membrane-bound TWEAK. FcγR-bound anti-Fn14 antibodies, however, activate the full spectrum of Fn14-associated activities. CONCLUSION Anti-Fn14 antibodies elicit agonistic activities differing from those of...

BACKGROUND Prior to the onset of human labour there is an increase in the synthesis of prostaglandins, cytokines and chemokines in the fetal membranes, particular the amnion. This is associated with activation of the transcription factor nuclear factor kappa B (NFκB). In this study we characterised the level of NFκB activity in amnion epithelial cells as a measure of amnion activation in sample...

APC = antigen presenting cell; cTEC = thymic cortical epithelial cell; DC = dendritic cell; IκB = inhibitory κB; IL = interleukin; mTEC = medullary thymic epithelial cell; NFκB = nuclear factor κB; NIK = NFκB inhibitory kinase; NOD = non-obese diabetic; NZB = New Zealand black; TLR = tolllike receptor; TNF = tumor necrosis factor; TRAF6 = TNF receptor associated factor 6. Arthritis Research & T...

Vascular smooth muscle cells (VSMCs) are indispensible components in foam cell formation. Salusin-β is a stimulator in the progression of atherosclerosis. Here, we showed that salusin-β increased foam cell formation evidenced by accumulation of lipid droplets and intracellular cholesterol content, and promoted monocyte adhesion in human VSMCs. Salusin-β increased the expressions and activity of...

Development of small molecule drug-like inhibitors blocking both nitric oxide synthase and NFκB could offer a synergistic therapeutic approach in the prevention and treatment of inflammation and cancer. During the course of evaluating the biological potential of a commercial compound library, 2-phenylindole (1) displayed inhibitory activity against nitrite production and NFκB with IC(50) values...

Aegle marmelos, is a medicinal plant from India, used for treating cancer-related symptoms in the Indian system of medicine. Its leaf, root, bark, seed and fruits are valued highly as Ayurvedic medicine. In the present study, the active fraction of Aegle marmelos was found to induce apoptosis in Hep G2 cells through NFκB deactivation followed by activation of proapoptotic factor p53. To evaluat...

The notch signaling pathway is highly conserved and plays an important role in the regulation of cellular proliferation, differentiation and apoptosis. Constitutive activation of notch signaling results in excessive cellular proliferation and a wide range of malignan-cies. However, notch can also act as a tumor suppressor, and its inactivation has been associated with an increased risk of spont...

The notch signaling pathway is highly conserved and plays an important role in the regulation of cellular proliferation, differentiation and apoptosis. Constitutive activation of notch signaling results in excessive cellular proliferation and a wide range of malignan-cies. However, notch can also act as a tumor suppressor, and its inactivation has been associated with an increased risk of spont...

The p53 and NFκB sequence-specific transcription factors play crucial roles in cell proliferation and survival with critical, even if typically opposite, effects on cancer progression. To investigate a possible crosstalk between p53 and NFκB driven by chemotherapy-induced responses in the context of an inflammatory microenvironment, we performed a proof of concept study using MCF7 cells. Transc...