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A growing number of findings highlight the crucial role of metabolic reprogramming in macrophage activation. Metabolic pathways are closely interconnected and recent literature demonstrates the need for glucose metabolism in anti-inflammatory as well as inflammatory macrophages. Moreover, fatty acid oxidation (FAO) not only supports anti-inflammatory responses as described formerly but also drives...
Activated macrophages undergo metabolic reprogramming, which drives their pro-inflammatory phenotype, but the mechanistic basis for this remains obscure. Here, we demonstrate that upon lipopolysaccharide (LPS) stimulation, macrophages shift from producing ATP by oxidative phosphorylation to glycolysis while also increasing succinate levels. We show that increased mitochondrial oxidation of succinate...
Introduction Activation of the inflammasome has been implicated in the pathology of various autoinflammatory and autoimmune diseases. While the NLRP3 inflammasome has been linked to arthritis progression, little is known about its synovial regulation or contribution to joint histopathology. Regulators of inflammation activation, such as interleukin (IL)-10, may have the potential to limit the inflammasome-driven...
The induction of the immediate-early genes coding for Interleukin 1β (IL1B) and Tumor Necrosis Factor α (TNF) is dependent upon Toll-Like receptor 4 (TLR4) detection of bacterial lipopolysaccharide (LPS). We have observed various distinctions for these genes that correlate with RNA Polymerase II (Pol II) pausing, specific transcription factor involvement, promoter architecture and histone epigenetics...
MicroRNA-155 (miR-155) is highly expressed in many cancers such as B cell lymphomas and myeloid leukemia, and inflammatory disorders such as rheumatoid arthritis, atopic dermatitis and multiple sclerosis. The role of miR-155 as both a promoter of inflammation and an oncogenic agent provides a clear need for miR-155 itself to be stringently regulated. We have recently found that the immunomodulatory...
IL10 is a pluripotent cytokine that has multiple functions on cells of the immune system. In most cases, IL10 acts as an anti-inflammatory cytokine, dampening the inflammatory response by down-regulating a subset of pro-inflammatory genes induced by TLR signalling. In B cells, IL10 appears to have an additional role enhancing proliferation, differentiation and class-switch recombination required for...
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