Mutations in human LPIN2 produce a disease known as Majeed syndrome, the clinical manifestations of which are ameliorated by strategies that block IL-1β or its receptor. However role lipin-2 during production remains elusive. We show here controls excessive formation primary and mouse macrophages several mechanisms, including activation inflammasome NLRP3. Lipin-2 regulates MAPK activation, mediates synthesis pro-IL-1β priming. also inhibits sensitization purinergic receptor P2X7 K+ efflux,...

Lipin-2 is a member of the lipin family enzymes, which are key effectors in biosynthesis lipids. Mutations human lipin-2 gene associated with inflammatory-based disorders; however, role cells immune system remains obscure. In this study, we have investigated proinflammatory action saturated fatty acids murine and macrophages. Depletion promotes increased expression genes Il6, Ccl2, Tnfα, depends on overstimulation JNK1/c-Jun pathway by acids. contrast, overexpression reduces release factors....

The lipins have been described as metabolic enzymes that regulate lipid biosynthesis and also signaling processes by controlling the cellular concentration of bioactive lipids, phosphatidic acid, diacylgycerol. In present work we studied subcellular localization role lipin-1 in human monocyte-derived macrophages. Human macrophages express isoforms α β. A transfected lipin-1α-enhanced GFP construct associates with membranes organelles can be stained Nile Red. Colocalization experiments...

Recent studies have highlighted the role of palmitoleic acid [16:1n-7 (cis-9-hexadecenoic acid)] as a lipid hormone that coordinates cross-talk between liver and adipose tissue exerts anti-inflammatory protective effects on hepatic steatosis insulin signaling in murine models metabolic disease. More recently, 16:1n-7 isomer, cis-7-hexadecenoic (16:1n-9), also possesses marked effects, has been described human circulating monocytes monocyte-derived macrophages. By using gas...

Abstract Lipin-1 is a Mg2+-dependent phosphatidic acid phosphatase involved in the de novo synthesis of phospholipids and triglycerides. Using macrophages from lipin-1–deficient animals human deficient enzyme, we show this work that acts as proinflammatory mediator during TLR signaling development vivo inflammatory processes. After TLR4 stimulation showed decreased production diacylglycerol activation MAPKs AP-1. Consequently, generation cytokines like IL-6, IL-12, IL-23, or enzymes...

Eicosanoids are a broad family of lipids that play critical role in host defense against bacterial and fungal infections. The first enzyme the metabolic pathway for generation eicosanoids is group IVA phospholipase A(2), also known as cytosolic A(2)alpha (cPLA(2)alpha). During phagocytosis, cPLA(2)alpha has been found to translocate phagosome, although molecular mechanism involved such translocation not elucidated. By using enhanced GFP-tagged proteins we show this work nonphosphorylatable...

Activation of macrophages with stimuli the innate immune response results in intense remodeling arachidonate-containing phospholipids, leading to mobilization large quantities this fatty acid for conversion into biologically active eicosanoids. As a consequence process, arachidonate levels membrane phospholipids markedly decrease. We have applied mass spectrometry-based lipid profiling study under inflammatory activation macrophages. identify an unusual inositol phospholipid molecule,...

Positional isomers of hexadecenoic acid are considered as fatty acids with anti-inflammatory properties. The best known them, palmitoleic (cis-9-hexadecenoic acid, 16:1n-7), has been identified a lipokine important beneficial actions in metabolic diseases. Hypogeic (cis-7-hexadecenoic 16:1n-9) regarded possible biomarker foamy cell formation during atherosclerosis. Notwithstanding the importance these regulators inflammatory responses, very little is about regulation their levels and...

Colon cancer is a devastating illness that associated with gut inflammation. Here, we explored the possible role of lipin-1, phosphatidic acid phosphatase, in development colitis-associated tumorigenesis. Azoxymethane and dextran sodium sulfate-treated (DSS-treated) animals deficient lipin-1 harbored fewer tumors carcinomas than WT due to decreased cellular proliferation, lower expression antiapoptotic protumorigenic factors, reduced infiltration macrophages colon tumors. They also displayed...

Abstract Polyamines contribute to several physiological and pathological processes, including cardiac hypertrophy in experimental animals. This involves an increase ornithine decarboxylase ( ODC ) activity intracellular polyamines associated with cyclic adenosine monophosphate cAMP increases. The aim of the study was establish role these human heart living patients. For this, (by high performance liquid chromatography) N 1 ‐acetylpolyamine oxidases APAO were determined right atrial appendage...

Human monocytes exposed to free arachidonic acid (AA), a secretory product of endothelial cells, acquire foamy phenotype which is due the accumulation cytoplasmic lipid droplets with high AA content. Recruitment inflamed endothelium contributes development atherosclerotic lesions. In this work, we investigated potential role stored in neutral lipids be cleaved by lipases and contribute mediator signaling. To end, used mass spectrometry-based lipidomic approaches combined strategies generate...

Androgens produce acute vasodilation of systemic, pulmonary, and coronary arteries in several mammal preparations increase cardiomyocyte contractility. A decrease the spontaneous beating sinoatrial cells has also been described. The aim this study was to characterize direct effect 5α-dihydrotestosterone on chronotropism inotropism same preparation as an approach establish cardiac output their mechanism action. effects were studied isolated right atria Wistar rats placed organ bath Tyrode...

Exposure to Gram-negative bacterial LPS exacerbates host immune responses and may lead sepsis, a life-threatening condition. Despite its high mortality morbidity, no drugs specifically directed treating sepsis are currently available. Using human cell genetic depletion, pharmacological inhibition, live-cell microscopy organelle-targeted molecular sensors we present evidence that the channel TRPC3 is activated intracellularly during macrophage exposure essential for Ca2+ release from internal...

Interferons (IFN) are crucial antiviral and immunomodulatory cytokines that exert their function through the regulation of a myriad genes, many which not yet characterized. Here, we reveal lipin-2, phosphatidic acid phosphatase whose mutations produce an autoinflammatory syndrome known as Majeed in humans, is regulated by IFN STAT-1-dependent manner. Lipin-2 inhibits viral replication both vitro vivo. Moreover, lipin-2 also acts regulator inflammation context reducing signaling TLR3...

Lipins are Mg2+‐dependent phosphatidic acid phosphatases involved in the de novo synthesis of phospholipids and triglycerides. Although they regulate cellular levels important signaling lipids, little is known about role lipins immune response. Using lipin‐1‐deficient animals, we show this work that phosphatase acts as a proinflammatory modulator during TLR also development vivo inflammatory processes. After stimulation with lipopolysaccharide (LPS), lipin‐1 deficient macrophages had...