Using macrophages from lipin-1-deficient animals and human macrophages deficient in the enzyme, we have found that this phosphatase acts as a proinflammatory mediator during TLR signaling and during the development of in vivo inflammatory processes. After TLR4 stimulation lipin-1 deficient macrophages showed a decreased production of diacylglycerol, activation of mitogenactivated protein kinase...

Abstract Lipid-metabolizing enzymes are important targets for small-molecule inhibitor discovery as the regulation of inflammation responses have been linked to lipid metabolism cascades controlled by these enzymes. Non-steroidal anti-inflammatory drugs inhibit in COX pathway preventing conversion arachidonic acid (AA) into inflammation-inducing prostaglandins. An upstream precursor AA is endoc...

Downregulation of drug metabolizing enzymes and transporters by proinflammatory mediators in hepatocytes, enterocytes renal tubular epithelium is an established mechanism affecting pharmacokinetics. Emerging evidences indicate that vascular endothelial cell expression may regulate pharmacokinetic pathways heart to modulate local bioavailability toxicity. However, whether inflammation regulates ...

Hypoxia and HIFs (HIF-1α and HIF-2α) modulate innate immune responses in the setting of systemic inflammatory responses and sepsis. The HIF prolyl hydroxylase enzymes PHD1, PHD2 and PHD3 regulate the mammalian adaptive response to hypoxia; however, their significance in the innate immune response has not been elucidated. We demonstrate in this study that deficiency of PHD3 (PHD3(-/-)) specifica...

Atherosclerotic plaque rupture and subsequent thrombosis is the main cause of sudden coronary death. Remarkably, atherosclerosis only develops in certain predisposed areas of the vasculature. Endothelial cells in these predisposed areas experience low or oscillatory shear stress, which activates the proinflammatory and procoagulant transcription factors activator protein 1 (AP-1) and nuclear fa...

Rheumatoid arthritis is a destructive arthropathy characterized by chronic synovial inflammation that imposes a substantial socioeconomic burden. Under the influence of the proinflammatory milieu, synovial fibroblasts (SFs), the main effector cells in disease pathogenesis, become activated and hyperplastic, releasing proinflammatory factors and tissue-remodeling enzymes. This study shows that a...

results aβ (1-42) stimulated the production of the proinflammatory cytokines il6, il1β, tnfα, and il18 in both the primary microglia cell culture and the b92 cell line. both the raav-il4 construct and the ril-4 protein were found to inhibit production of the most important aβ (1-42)-induced proinflammatory cytokine mrnas in the two types of cells with different patterns. conclusions it seems th...

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease characterized by inflammatory cell infiltration, synovial inflammation, and cartilage destruction. Proliferative fibroblast-like synoviocytes (FLS) play crucial roles in both propagation of inflammation and joint damage because of their production of great amount of proinflammatory cytokines and proteolytic enzymes. In this st...