ceramide TGf-beta

Background: Atopic eczema is an itchy inflammatory disorder characterised by skin barrier dysfunction. Loss-of-function mutations in the gene encoding filaggrin ( FLG ) are a major risk factor, but the mechanisms by which filaggrin haploinsufficiency leads to atopic inflammation remain incompletely understood. Skin as an organ that can be modelled using primary cells in vitro provides the opportunity for selected genetic effects to be investigated in detail. Methods: Primary human keratinocytes and donor-matched primary fibroblasts from healthy individuals were used to create skin organoid models with and without siRNA-mediated knockdown of FLG ...

BACKGROUND: Non-alcoholic steatohepatitis (NASH) is a common disease and feeding mice a methionine-choline-deficient (MCD) diet is a frequently used model to study its pathophysiology. Genetic and environmental factors influence NASH development and liver lipid content, which was studied herein using C57BL/6 J mice bred in two different animal facilities. METHODS: Age-matched male C57BL/6 J mice bred in two different animal facilities (later on referred to as WT1 and WT2) at the University Hospital of Regensburg were fed identical MCD or control chows for 2 weeks...

Endogenous bone marrow-derived mesenchymal stem cells (BM-MSCs) are mobilized into peripheral blood and injured tissues by various growth factors and cytokines that are expressed in the injured tissues, such as substance P (SP), stromal cell derived factor-1 (SDF-1), and transforming growth factor-beta (TGF-β). Extracellular bioactive lipid metabolites such as ceramide-1-phosphate and sphingosine-1-phosphate also modulate BM-MSC migration as SP, SDF-1, and TGF-β. However, the roles of intrinsic lipid kinases of BM-MSCs in the stem cell migration are unclear...

This data article provides gene expression profiles, determined by using real-time PCR, of fibroblasts and keratinocytes treated with 0.01% and 0.001% extracts of holy basil plant ( Ocimum tenuiflorum ), sri lankan local name "maduruthala", 0.1% and 0.01% extracts of malabar nut plant ( Justicia adhatoda ), sri lankan local name "adayhoda" and 0.003% and 0.001% extracts of emblic myrobalan plant ( Phyllanthus emblica ), sri lankan local name "nelli", harvested in Sri Lanka. For fibroblasts, the dataset includes expression profiles for genes encoding hyaluronan synthase 1 (HAS1), hyaluronan synthase 2 (HAS2), hyaluronidase-1 (HYAL1), hyaluronidase-2 (HYAL2), versican, aggrecan, CD44, collagen, type I, alpha 1 (COL1A1), collagen, type III, alpha 1 (COL3A1), collagen, type VII, alpha 1 (COL7A1), matrix metalloproteinase 1 (MMP1), acid ceramidase, basic fibroblast growth factor (bFGF), fibroblast growth factor-7 (FGF7), vascular endothelial growth factor (VEGF), interleukin-1 alpha (IL-1α), cyclooxygenase-2 (cox2), transforming growth factor beta (TGF-β), and aquaporin 3 (AQP3)...

This data article provides gene expression profiles, determined by using real-time PCR, of fibroblasts and keratinocytes treated with 0.01% and 0.001% extracts of neem plant (Azadirachta indica), local name "Kohomba" in Sri Lanka, harvested in Sri Lanka. For fibroblasts, the dataset includes expression profiles for genes encoding hyaluronan synthase 1 (HAS1), hyaluronan synthase 2 (HAS2), hyaluronidase-1 (HYAL1), hyaluronidase-2 (HYAL2), versican, aggrecan, CD44, collagen, type I, alpha 1 (COL1A1), collagen, type III, alpha 1 (COL3A1), collagen, type VII, alpha 1 (COL7A1), matrix metalloproteinase 1 (MMP1), acid ceramidase, basic fibroblast growth factor (bFGF), fibroblast growth factor-7 (FGF7), vascular endothelial growth factor (VEGF), interleukin-1 alpha (IL-1α), cyclooxygenase-2 (cox2), transforming growth factor beta (TGF-β), and aquaporin 3 (AQP3)...

Alternative medicines are commonly used for the disease prevention and treatment worldwide. Aristolochic acid (AAI) nephropathy (AAN) is a common and rapidly progressive interstitial nephropathy caused by ingestion of Aristolochia herbal medications. Available data on pathophysiology and molecular mechanisms of AAN are limited and were explored here. SD rats were randomized to AAN and control groups. AAN group was treated with AAI by oral gavage for 12 weeks and observed for additional 12 weeks. Kidneys were processed for histological evaluation, Western blotting, and metabolomics analyses using UPLC-QTOF/HDMS...

Connective tissue growth factor (CTGF) is known to be involved in retinal fibrotic disorders. We used human retinal pigment epithelial cells (HRPE), which play critical roles in retinal fibrosis, to examine the expression of CTGF and its regulation by ceramide and TGF-β. Real-time PCR analysis showed downregulation of CTGF mRNA by C2 ceramide and upregulation by TGF-β. C2 ceramide also inhibited constitutive and TGF-β-enhanced CTGF secretion by HRPE cells. Predominant secretion (>80% of total) of CTGF from the apical side was observed in highly polarized HRPE cells...

Ceramides, sphingosine-based lipid molecules, are generated mainly from the hydrolysis of sphingomyelin and play pivotal roles in biological processes including cell growth, differentiation, and inflammation. In this study, we investigated the effect of exogenous ceramides on the differentiation of regulatory T (Treg) cells and expression of FoxP3 gene in Treg cells. A cell-permeable C6-ceramide (C6) was capable of upregulating Treg cell differentiation when acting together with transforming growth factor-beta (TGF-β), and this induction was independent of T-cell receptor (TCR) and CD28 strength...

Hypoxemic respiratory failure of the neonatal organism involves increased acid sphingomyelinase (aSMase) activity and production of ceramide, a second messenger of a pro-inflammatory pathway that promotes increased vascular permeability, surfactant alterations and alveolar epithelial apoptosis. We comparatively assessed the benefits of topical aSMase inhibition by either imipramine (Imi) or phosphatidylinositol-3,5-bisphosphate (PIP2) when administered into the airways together with surfactant (S) for fortification...

BACKGROUND AND AIMS: Glycolipids have been shown to serve specialized functions in cell signalling, proliferation and differentiation processes, which are all important during liver regeneration. We previously generated beta-glucosidase 2 (GBA2) knockout mice that accumulate the glycolipid glucosylceramide in various tissues, including the liver. The present study addressed the role of GBA2-deficiency and subsequent glucosylceramide accumulation in liver regeneration. METHODS: Gba2 knockout and wild-type mice were subjected to two-third partial hepatectomy...

A growing body of evidence demonstrates a correlation between Th2 cytokines and the development of focal and segmental glomerulosclerosis (FSGS). Therefore, we hypothesized that GSL-1, a monoglycosylceramide from Sphingomonas ssp. with pro-Th1 activity on invariant Natural Killer T (iNKT) lymphocytes, could counterbalance the Th2 profile and modulate glomerulosclerosis. Using an adriamycin(ADM)-based model of FSGS, we found that BALB/c mice presented albuminuria and glomerular degeneration in association with a Th2-like pro-fibrogenic profile; these mice also expressed a combination of inflammatory cytokines, such as IL-4, IL-1α, IL-1β, IL-17, TNF-α, and chemokines, such as RANTES and eotaxin...

UNLABELLED: Lithocholic acid (LCA) is an endogenous compound associated with hepatic toxicity during cholestasis. LCA exposure in mice resulted in decreased serum lysophosphatidylcholine (LPC) and sphingomyelin levels due to elevated lysophosphatidylcholine acyltransferase (LPCAT) and sphingomyelin phosphodiesterase (SMPD) expression. Global metabolome analysis indicated significant decreases in serum palmitoyl-, stearoyl-, oleoyl-, and linoleoyl-LPC levels after LCA exposure. LCA treatment also resulted in decreased serum sphingomyelin levels and increased hepatic ceramide levels, and induction of LPCAT and SMPD messenger RNAs (mRNAs)...

BACKGROUND: The role of inflammation in the pathogenesis of non-alcoholic steatohepatitis (NASH), a common cause of liver disease, is still poorly understood. This study aimed at assessing the involvement of a major inflammatory cytokine, IL-6, in NASH. MATERIALS AND METHODS: Steatohepatitis was induced by feeding wild-type or IL-6(-/-) mice for 5 weeks with a methionine and choline-deficient (MCD) diet. RESULTS: Whereas MCD diet-induced weight loss and decreases in serum glucose, cholesterol and triglyceride levels were similar in both genotypes, serum alanine aminotransferase was less elevated in IL-6(-/-) mice than in wild-type animals...

Ceramides are used in skin care and treatment of dermatological diseases. Cell viability and extracellular matrix (ECM) remodeling are important parameters in skin health. Skin photoaging, from exposure to ultraviolet radiation, is associated with epidermal hyperplasia and dermal ECM atrophy caused by alterations in expression of matrixmetalloproteinases (MMPs), elastin and transforming growth factor-beta (TGF-beta). The purpose of this study was to determine the effects of c2-ceramide (ceramide) on the cell viability and expression of TGF-beta, MMP-1 and elastin in cultured keratinocytes and fibroblasts...

UNLABELLED: Natural killer T (NKT) cells and regulatory T cells (Tregs) are both found within the liver and are known to exhibit immune regulatory functions. Hepatic NKT cells are activated early during inflammatory responses and release cytokines, including interferon gamma (IFN-gamma), which we speculated could regulate Treg recruitment to the liver. To examine this, we treated C57BL/6 mice with a specific NKT cell activating ligand alpha galactosyl-C18-ceramide (alphaGal-C18-Cer) and examined the hepatic recruitment of Tregs...

TTF-1 [thyroid transcription factor-1; also known as Nkx2.1, T/EBP (thyroid-specific-enhancer-binding protein) or TITF1] is a homeodomain-containing transcription factor essential for the morphogenesis and differentiation of the thyroid, lung and ventral forebrain. TTF-1 controls the expression of select genes in the thyroid, lung and the central nervous system. In the lung, TTF-1 controls the expression of surfactant proteins that are essential for lung stability and lung host defence. Human TTF-1 is encoded by a single gene located on chromosome 14 and is organized into two/three exons and one/two introns...

Natural killer T (NKT) cells are known to produce Th17 cytokine IL-17 in addition to Th1/2 cytokines. In this study, the ability of NKT cells to produce IL-22, another Th17 cytokine, was examined in mice. When murine spleen cells were stimulated with alpha-galactosyl ceramide, a ligand for NKT cells, not only Th1/2 cytokines (IFN-gamma, IL-4) but Th17 cytokines (IL-17, IL-22) were produced. NKT cells isolated from splenocytes released IL-17 and IL-22 following CD3, CD3/IL-2 or CD3/CD28 stimulation, in which CD3/CD28 costimulation was most effective...

We examined the role of sphingosine kinase-1 (SphK1), a critical regulator of the ceramide/sphingosine 1-phosphate (S1P) biostat, in the regulation of death and survival of SH-SY5Y neuroblastoma cells in response to amyloid beta (Abeta) peptide (25-35). Upon incubation with Abeta, SH-SY5Y cells displayed a marked down-regulation of SphK1 activity coupled with an increase in the ceramide/S1P ratio followed by cell death. This mechanism was redox-sensitive; N-acetylcysteine totally abrogated the down-regulation of SphK1 activity and strongly inhibited Abeta-induced cell death...

Although NKT cells has been known to exert protective roles in the development of autoimmune diseases, the functional roles of NKT cells in the downstream events of antibody-induced joint inflammation remain unknown. Thus, we explored the functional roles of NKT cells in antibody-induced arthritis using the K/BxN serum transfer model. NKT cell-deficient mice were resistant to the development of arthritis, and wild-type mice administrated with alpha-galactosyl ceramide, a potent NKT cell activator, aggravated arthritis...

Transforming growth factor-beta (TGF-beta) signaling plays a pivotal role in extracellular matrix deposition by stimulating collagen production and other extracellular matrix proteins and by inhibiting matrix degradation. The present study was undertaken to define the role of sphingosine kinase (SphK) in TGF-beta signaling. TGF-beta markedly up-regulated SphK1 mRNA and protein amounts and caused a prolonged increase in SphK activity in dermal fibroblasts. Concomitantly, TGF-beta reduced sphingosine-1-phosphate phosphatase activity...