Ceramide inflammation

Many intracellular pathogens structurally disrupt the Golgi apparatus as an evolutionarily conserved promicrobial strategy. Yet, the host factors and signaling processes involved are often poorly understood, particularly for Anaplasma phagocytophilum , the agent of human granulocytic anaplasmosis. We found that A. phagocytophilum elevated cellular levels of the bioactive sphingolipid, ceramide-1-phosphate (C1P), to promote Golgi fragmentation that enables bacterial proliferation, conversion from its non-infectious to infectious form, and productive infection...

Chronic inflammation of adipose tissue is a prominent characteristic of many metabolic diseases. Lipid metabolism in adipose tissue is consistently dysregulated during inflammation, which is characterized by substantial infiltration by proinflammatory cells and high cytokine concentrations. Adipose tissue inflammation is caused by a variety of endogenous factors, such as mitochondrial dysfunction, reactive oxygen species (ROS) production, endoplasmic reticulum (ER) stress, cellular senescence, ceramides biosynthesis and mediators of lipopolysaccharides (LPS) signaling...

Inflammatory bowel disease (IBD), characterized by chronic inflammation in the intestinal tract, increases the risk for the development of colorectal cancer (CRC). Sphingolipids, which have been implicated in IBD and CRC, are a class of bioactive lipids that regulate cell signaling, differentiation, apoptosis, inflammation, and survival. The balance between ceramide (Cer), the central sphingolipid involved in apoptosis and differentiation, and sphingosine-1-phosphate (S1P), a potent signaling molecule involved in proliferation and inflammation, is vital for the maintenance of normal cellular function...

High-dose irradiation can trigger numerous endothelial dysfunctions, including apoptosis, the overexpression of adhesion molecules, and alteration of adherens junctions. Altogether, these endothelial dysfunctions contribute to the development of tissue inflammation and organ damage. The development of endothelial dysfunctions may depend on protein phosphorylation by various protein kinases, but the possible role of protein kinase A (PKA) has not been investigated so far, and efficient compounds able to protect the endothelium from irradiation effects are needed...

Interleukin-10 (IL-10) is a key anti-inflammatory cytokine that can limit immune cell activation and cytokine production in innate immune cell types1 . Loss of IL-10 signalling results in life-threatening inflammatory bowel disease in humans and mice-however, the exact mechanism by which IL-10 signalling subdues inflammation remains unclear2-5 . Here we find that increased saturated very long chain (VLC) ceramides are critical for the heightened inflammatory gene expression that is a hallmark of IL-10 deficiency...

The global prevalence of type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) is rapidly increasing, revealing a strong association between these two diseases. Currently, there are no curative medication available for the comorbidity of T2DM and AD. Ceramides are structural components of cell membrane lipids and act as signal molecules regulating cell homeostasis. Their synthesis and degradation play crucial roles in maintaining metabolic balance in vivo , serving as important mediators in the development of neurodegenerative and metabolic disorders...

Cold stored platelets (CS) are once again being reintroduced for clinical use. Transfused CS offer benefits over room temperature stored platelets (RTS) such as increased hemostatic effects and prolongation of shelf-life. Despite these advantages little is known about their association with transfusion-related acute lung injury (TRALI). TRALI is associated with prolonged storage RTS and has a mortality of > 15%. Determining the safety of CS is important considering their proposed use in TRALI-vulnerable populations with systemic inflammation such as surgical or trauma patients...

BACKGROUND: Gouty arthritis (GA) is a common inflammatory disease caused by deposition of monosodium urate (MSU) crystals in diarthrodial joints. GA attacks commonly involved in joint with red, swollen, heat and pain, and often happened in unilateral foot-first metatarsophalangeal. Accumulated studies have proved that lipids play critical roles in biological processes and lipids biomarkers can substitute for the diagnosis of various diseases. METHODS: Herein, shotgun lipidomics was used to quantitatively analyze serum lipidomes of a gouty model which was induced by injecting MSU crystals and feeding high-fat diet with/without treatment with allopurinol...

OBJECTIVE: Skin barrier defects are one of the primary causes of atopic dermatitis (AD). The basis of skin barrier defects in AD is due to a deficiency in various barrier proteins including filaggrin, involucrin, claudins, and lipids such as ceramide, fatty acids, and cholesterol. This review updates a more detailed lipid dysregulation in the skin barrier of AD based on recent lipidomic analysis. The clinical implications, treatments, prevention, and predictive capability of skin barrier defects are also reviewed...

PURPOSE OF REVIEW: The primary aim of this review is to provide an in-depth examination of the role bioactive lipids-namely lysophosphatidic acid (LPA) and ceramides-play in inflammation-mediated cardiac remodeling during heart failure. With the global prevalence of heart failure on the rise, it is critical to understand the underlying molecular mechanisms contributing to its pathogenesis. Traditional studies have emphasized factors such as oxidative stress and neurohormonal activation, but emerging research has shed light on bioactive lipids as central mediators in heart failure pathology...

Although sickle cell disease (SCD) and its manifestations have been associated with various lipid alterations, there are a few studies exploring the impact of sphingolipids in SCD. In this study, we determined plasma ceramide (Cer) and sphingomyelin (CerPCho) species and investigated their association with the crisis in SCD. SCD patients (N = 27) suffering from vaso-occlusive crisis (VOC) or acute chest syndrome (ACS) were involved in this study. Blood samples were drawn at crisis and later at steady state periods...

The nerve injury induced protein 2 (NINJ2) belongs to a family of homophilic adhesion molecules and was initially found to be involved in nerve regeneration. However, the role of NINJ2 in other cellular process are not well studied. Here, by generating a Ninj2-deficient mouse model, we showed that mice deficient in Ninj2 have a short lifespan and are prone to spontaneous tumors, systemic inflammation and metabolic defects. To better understand the metabolic traits that contributes to these phenotypes, we performed comprehensive carbohydrate and lipid metabolic analyses...

One of the major global health and welfare issues is the treatment of obesity and associated metabolic disorders, such as type 2 diabetes mellitus and nonalcoholic fatty liver disease. Obesity, caused by the excessive accumulation of triglycerides in adipose tissues, induces adipocyte dysfunction, followed by inflammation, in adipose tissues and lipotoxicity in nonadipose tissues. Several studies have shown that obesity and glucose homeostasis are influenced by sphingolipid mediators, including ceramide and sphingosine 1-phosphate (S1P)...

Vesicating chemicals like sulfur mustard (SM) or nitrogen mustard (NM) can cause devastating damage to the eyes, skin, and lungs. Eyes, being the most sensitive, have complicated pathologies that can manifest immediately after exposure (acute) and last for years (chronic). No FDA-approved drug is available to be used as medical counter measures (MCMs) against such injuries. Understanding the pathological mechanisms in acute and chronic response of the eye is essential for developing effective MCMs. Here, we report the clinical and histopathological characterization of a mouse model of NM-induced ocular surface injury (entire surface) developed by treating the eye with 2% ( w / v ) NM solution for 5 min...

Coronary atherosclerosis is caused by plaque build-up, with lipids playing a pivotal role in its progression. However, lipid composition and distribution within coronary atherosclerosis remain unknown. This study aims to characterize lipids and investigate differences in lipid composition across disease stages to aid in the understanding of disease progression. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) was used to visualize lipid distributions in coronary artery sections (n=17) from hypercholesterolemic swine...

Extracellular vesicles (EVs) have a significant impact on the pathophysiological processes associated with various diseases such as tumors, inflammation, and infection. They exhibit molecular, biochemical, and entry control characteristics similar to viral infections. Viruses, on the other hand, depend on host metabolic machineries to fulfill their biosynthetic requirements. Due to potential advantages such as biocompatibility, biodegradation, and efficient immune activation, EVs have emerged as potential therapeutic targets against the SARS-CoV-2 infection...

Non-alcoholic fatty liver disease (NAFLD) is projected to be the most common chronic liver disease worldwide and is closely linked to obesity, insulin resistance and type 2 diabetes. Currently, no pharmacological treatments are available to treat NAFLD, and lifestyle modification, including dietary interventions, is the only remedy. Therefore, we conducted a study to determine whether supplementation with medium-chain triglycerides (MCTs), containing a mixture of C8 and C10 (60/40), attenuates NAFLD in obese and insulin-resistant mice...

The protective effects of wheat ceramide powder (WC-P) on ultraviolet B (UVB)-induced skin oxidative stress and photoaging in hairless mice were investigated in this study. Moreover, the activities of antioxidant enzymes, inflammation, wrinkle formation-related pathway, and moisturizing capacity were evaluated. Mice were randomly divided into six groups (n=8): normal control (non-UVB irradiation), control (UVB irradiation), L-ascorbic acid [positive control, UVB irradiation with dietary supplementation of L-ascorbic acid at 100 mg/kg/body weight (bw)], WC-P5 (UVB irradiation with dietary supplementation of WC-P at 5 mg/kg/bw), WC-P20 (UVB irradiation with dietary supplementation of WC-P at 20 mg/kg/bw), and WC-P40 (UVB irradiation with dietary supplementation of WC-P at 40 mg/kg/bw)...

Ketogenic diets (KDs) are very high-fat low-carbohydrate diets that promote nutritional ketosis and are widely used for weight loss, although concerns about potential adverse cardiovascular effects remain. We investigated a very high-fat KD's vascular impact and plasma metabolic signature compared to a non-ketogenic high-fat diet (HFD). Apolipoprotein E deficient (ApoE -/- ) mice were fed a KD (%kcal:81:1:18, fat/carbohydrate/protein), a non-ketogenic high-fat diet with half of the fat content (HFD) (%kcal:40:42:18, fat/carbohydrate/protein) for 12 weeks...

Traditional research in inflammatory dermatoses has relied on animal models and reconstructed human epidermis to study these conditions. However, these models are limited in replicating the complexity of real human skin and reproducing the intricate pathological changes in skin barrier components and lipid profiles. To address this gap, we developed experimental models that mimic various human inflammatory skin phenotypes. Human ex vivo skins were stimulated with various triggers, creating models for inflammation-induced angiogenesis, irritation response, and chronic T-cell activation...