scholarly journals De novo ceramide synthesis is involved in acute inflammation during labor

2016 ◽  
Vol 397 (2) ◽  
pp. 147-155 ◽  
Author(s):  
Paola Signorelli ◽  
Laura Avagliano ◽  
Marta R. Reforgiato ◽  
Nadia Toppi ◽  
Josefina Casas ◽  
...  
Keyword(s):  
Inflammatory Process ◽  
De Novo ◽  
Inflammatory Responses ◽  
Inflammatory Marker ◽  
Labor Duration ◽  
Vaginal Deliveries ◽  
Ceramide Synthesis ◽  
Elective Cesarean ◽  
Stress Signals ◽  
Membrane Components

Abstract Gestation is regulated by an inflammatory process that allows implantation and parturition. The comprehension of such inflammatory switches is important for the identification of therapeutic targets in pregnancy defects. Sphingolipids are a class of structural membrane components with important signaling functions. Among sphingolipids, ceramide is a well-known mediator of stress signals and pro-inflammatory responses. In this paper, we evaluated the association between ceramide increase and the inflammatory process of labor, comparing placentas from vaginal deliveries, including both spontaneous and induced labor, versus elective cesarean. We demonstrated that: (i) the inflammatory marker IL-6 is upregulated in labored placentas; (ii) IL-6 content inversely correlates with labor duration; (iii) ceramide content and expression of serine palmitoyl transferase (SPT, rate limiting enzyme for de novo ceramide synthesis) are increased in labored placentas; (iv) the expression of SPT directly correlates with inflammation and inversely with labor duration. These observations suggest that ceramide metabolism and signaling may be implicated in controlling important inflammatory mechanisms driving gestation: we hypothesize that ceramide can be a therapeutic target in inflammatory complications of parturition.

scholarly journals A Consideration of Biomarkers to be Used for Evaluation of Inflammation in Human Nutritional Studies

2013 ◽  
Vol 109 (S1) ◽  
pp. S1-S34 ◽  
Author(s):  
P.C. Calder ◽  
N. Ahluwalia ◽  
R. Albers ◽  
N. Bosco ◽  
R. Bourdet-Sicard ◽  
...  
Keyword(s):  
Inflammatory Markers ◽  
Inflammatory Process ◽  
Inflammatory Responses ◽  
Task Force ◽  
Inflammatory Marker ◽  
Low Grade ◽  
Future Health ◽  
Modifying Factors ◽  
Markers Of Inflammation ◽  
Nutritional Studies

To monitor inflammation in a meaningful way, the markers used must be valid: they must reflect the inflammatory process under study and they must be predictive of future health status. In 2009, the Nutrition and Immunity Task Force of the International Life Sciences Institute, European Branch, organized an expert group to attempt to identify robust and predictive markers, or patterns or clusters of markers, which can be used to assess inflammation in human nutrition studies in the general population. Inflammation is a normal process and there are a number of cells and mediators involved. These markers are involved in, or are produced as a result of, the inflammatory process irrespective of its trigger and its location and are common to all inflammatory situations. Currently, there is no consensus as to which markers of inflammation best represent low-grade inflammation or differentiate between acute and chronic inflammation or between the various phases of inflammatory responses. There are a number of modifying factors that affect the concentration of an inflammatory marker at a given time, including age, diet and body fatness, among others. Measuring the concentration of inflammatory markers in the bloodstream under basal conditions is probably less informative compared with data related to the concentration change in response to a challenge. A number of inflammatory challenges have been described. However, many of these challenges are poorly standardised. Patterns and clusters may be important as robust biomarkers of inflammation. Therefore, it is likely that a combination of multiple inflammatory markers and integrated readouts based upon kinetic analysis following defined challenges will be the most informative biomarker of inflammation.

scholarly journals Anti-NLRP3 Inflammasome Natural Compounds: An Update

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 136
Author(s):  
Baolong Liu ◽  
Jiujiu Yu
Keyword(s):  
Nlrp3 Inflammasome ◽  
Protein Complex ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Natural Compounds ◽  
Pyrin Domain ◽  
Inflammatory Protein ◽  
Wide Range ◽  
Activation Mechanisms ◽  
Stress Signals

The nucleotide-binding domain and leucine-rich repeat related (NLR) family, pyrin domain containing 3 (NLRP3) inflammasome is a multimeric protein complex that recognizes various danger or stress signals from pathogens, the host, and the environment, leading to activation of caspase-1 and inducing inflammatory responses. This pro-inflammatory protein complex plays critical roles in pathogenesis of a wide range of diseases including neurodegenerative diseases, autoinflammatory diseases, and metabolic disorders. Therefore, intensive efforts have been devoted to understanding its activation mechanisms and to searching for its specific inhibitors. Approximately forty natural compounds with anti-NLRP3 inflammasome properties have been identified. Here, we provide an update about new natural compounds that have been identified within the last three years to inhibit the NLRP3 inflammasome and offer an overview of the underlying molecular mechanisms of their anti-NLRP3 inflammasome activities.

scholarly journals Anandamide Exerts a Differential Effect on Human Placenta Before and After the Onset of Labor

2021 ◽  
Vol 12 ◽  
Author(s):  
Paula Accialini ◽  
Cyntia Abán ◽  
Tomás Etcheverry ◽  
Mercedes Negri Malbrán ◽  
Gustavo Leguizamón ◽  
...  
Keyword(s):  
Cesarean Section ◽  
Vaginal Delivery ◽  
Endocannabinoid System ◽  
Cesarean Sections ◽  
Vaginal Deliveries ◽  
Before And After ◽  
Elective Cesarean ◽  
Main Components ◽  
Relevant Finding

The onset of labor involves the action of multiple factors and recent reports have postulated the endocannabinoid system as a new regulator of this process. Our objective was to study the role of anandamide, one of the main endocannabinoids, on the regulation of placental molecules that contribute to the onset of labor at term. Placental samples were obtained from patients with laboring vaginal deliveries and from non-laboring elective cesarean sections. Vaginal delivery placentas produced higher prostaglandins levels than cesarean section samples. Besides, no differences were observed in NOS basal activity between groups. Incubation of vaginal delivery placentas with anandamide increased prostaglandins concentration and decreased NOS activity. Antagonism of type-1cannabinoid receptor (CB1) did not alter the effect observed on NOS activity. Conversely, incubation of cesarean section placentas with anandamide reduced prostaglandins levels and enhanced NOS activity, the latter involving the participation of CB1. Furthermore, we observed a differential expression of the main components of the endocannabinoid system between placental samples, being the change in CB1 localization the most relevant finding. Our results suggest that anandamide acts as a modulator of the signals that regulate labor, exerting differential actions depending on CB1 localization in laboring or non-laboring term placentas.

scholarly journals Human T-cell lymphotropic virus type I-transformed T-cells have a partial defect in ceramide synthesis in response to N-(4-hydroxyphenyl)retinamide

2005 ◽  
Vol 392 (1) ◽  
pp. 231-239 ◽  
Author(s):  
Nadine Darwiche ◽  
Ghada Abou-Lteif ◽  
Tarek Najdi ◽  
Lina Kozhaya ◽  
Ahmad Abou Tayyoun ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Growth Inhibition ◽  
Virus Type ◽  
De Novo ◽  
Type I ◽  
De Novo Synthesis ◽  
Human T Cell ◽  
Ceramide Synthesis ◽  
Malignant T Cells

Treatment with the synthetic retinoid HPR [N-(4-hydroxyphenyl)-retinamide] causes growth arrest and apoptosis in HTLV-I (human T-cell lymphotropic virus type-I)-positive and HTLV-I-negative malignant T-cells [8]. It was observed that HPR-mediated growth inhibition was associated with ceramide accumulation only in HTLV-I-negative cells. The aim of the present study was to investigate the mechanism by which HPR differentially regulates ceramide metabolism in HTLV-I-negative and HTLV-I-positive malignant T-cells. Clinically achievable concentrations of HPR caused early dose-dependent increases in ceramide levels only in HTLV-I-negative cells and preceded HPR-induced growth suppression. HPR induced de novo synthesis of ceramide in HTLV-I-negative, but not in HTLV-I-positive, cells. Blocking ceramide glucosylation in HTLV-I-positive cells, which leads to accumulation of endogenous ceramide, rendered these cells more sensitive to HPR. Exogenous cell-permeant ceramides that function partially by generating endogenous ceramide induced growth suppression in all tested malignant lymphocytes, were consistently found to be less effective in HTLV-I-positive cells confirming their defect in de novo ceramide synthesis. Owing to its multipotent activities, the HTLV-I-encoded Tax protein was suspected to inhibit ceramide synthesis. Tax-transfected Molt-4 and HELA cells were less sensitive to HPR and C6-ceramide mediated growth inhibition respectively and produced lower levels of endogenous ceramide. Together, these results indicate that HTLV-I-positive cells are defective in de novo synthesis of ceramide and that therapeutic modalities that bypass this defect are more likely to be successful.

scholarly journals Monosodium Urate Microcrystals Induce Cyclooxygenase-2 in Human Monocytes

Blood ◽  
1998 ◽  
Vol 91 (5) ◽  
pp. 1769-1776 ◽  
Author(s):  
Marc Pouliot ◽  
Michael J. James ◽  
Shaun R. McColl ◽  
Paul H. Naccache ◽  
Leslie G. Cleland
Keyword(s):  
De Novo ◽  
Inflammatory Responses ◽  
Gouty Arthritis ◽  
Calcium Pyrophosphate ◽  
Mononuclear Phagocyte ◽  
Mononuclear Phagocytes ◽  
Mitogen Activated Protein Kinase ◽  
Calcium Pyrophosphate Dihydrate ◽  
Monosodium Urate ◽  
Cox 2

Abstract The formation and deposition of monosodium urate (MSU) microcrystals in articular and periarticular tissues is the causative agent of acute or chronic inflammatory responses known as gouty arthritis. Mononuclear phagocyte activation is involved in early triggering events of gout attacks. Because stimulated mononuclear phagocytes can constitute an important source of the inducible isoform of cyclooxygenase (COX-2), we evaluated the effects that proinflammatory microcrystals might have on COX-2 protein expression in crystal-stimulated monocytes. We found that MSU crystals, but not calcium pyrophosphate dihydrate (CPPD) crystals, induced COX-2, which correlated with the synthesis of prostaglandin E2 (PGE2) and thromboxane A2(TXA2). Crystal-induced de novo synthesis of COX-2 was dependent on transcriptional and translational events. Inhibition of tyrosine phosphorylation, by herbimycin A, blocked crystal-induced COX-2. Similarly, an inhibitor of the p38 mitogen-activated protein kinase, SB 203580, inhibited the stimulation of COX-2. Colchicine inhibited crystal-induced COX-2. In all cases, prostanoid synthesis was concomitantly inhibited. Taken together, these results implicate COX-2 in the development of MSU-induced inflammation.

scholarly journals Massage Therapy Modulates Inflammatory Mediators Following Sprint Exercise in Healthy Male Athletes

2020 ◽  
Vol 5 (1) ◽  
pp. 9
Author(s):  
Gillian E. White ◽  
Sarah L. West ◽  
Jessica E. Caterini ◽  
Alex P. Di Battista ◽  
Shawn G. Rhind ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Inflammatory Marker ◽  
Massage Therapy ◽  
Muscle Performance ◽  
Drop Jump ◽  
Healthy Male ◽  
Necrosis Factor Alpha ◽  
Male Athletes ◽  
Jump Performance ◽  
Baseline Levels

Massage therapy is a common postexercise muscle recovery modality; however, its mechanisms of efficacy are uncertain. We evaluated the effects of massage on systemic inflammatory responses to exercise and postexercise muscle performance and soreness. In this crossover study, nine healthy male athletes completed a high-intensity intermittent sprint protocol, followed by massage therapy or control condition. Inflammatory markers were assessed pre-exercise; postexercise; and at 1, 2, and 24 h postexercise. Muscle performance was measured by squat and drop jump, and muscle soreness on a Likert scale. Significant time effects were observed for monocyte chemoattractant protein-1 (MCP-1), interleukin-8 (IL-8), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor alpha (TNFα), drop jump performance, squat jump performance, and soreness. No significant effects for condition were observed. However, compared with control, inflammatory marker concentrations (IL-8, TNFα, and MCP-1) returned to baseline levels earlier following the massage therapy condition (p < 0.05 for all). IL-6 returned to baseline levels earlier following the control versus massage therapy condition (p < 0.05). No differences were observed for performance or soreness variables. MCP-1 area under the curve (AUC) was negatively associated with squat and drop jump performance, while IL-10 AUC was positively associated with drop jump performance (p < 0.05 for all). In conclusion, massage therapy promotes resolution of systemic inflammatory signaling following exercise but does not appear to improve performance or soreness measurements.

scholarly journals Transforming Growth Factor β and CD25 Are Important for Controlling Systemic Dissemination following Yersiniaenterocolitica Infection of the Gut

2010 ◽  
Vol 78 (9) ◽  
pp. 3716-3725 ◽  
Author(s):  
Youmin Zhong ◽  
Angelene Cantwell ◽  
Peter H. Dube
Keyword(s):  
Growth Factor ◽  
Autoimmune Disease ◽  
Bacterial Infection ◽  
Yersinia Enterocolitica ◽  
Transforming Growth Factor ◽  
De Novo ◽  
Inflammatory Responses ◽  
Acute Infection ◽  
Transforming Growth Factor Β ◽  
Mesenteric Lymph Nodes

ABSTRACT Infection of the gut by invasive bacterial pathogens leads to robust inflammatory responses that if left unchecked can lead to autoimmune disease and other sequelae. How the immune system controls inflammation and limits collateral damage to the host during acute bacterial infection is poorly understood. Here, we report that antibody-mediated neutralization of transforming growth factor β (TGF-β) prior to infection with the model enteric pathogen Yersinia enterocolitica reduces the mean time to death by 1 day (P = 0.001), leads to rapid colonization of the liver and lung, and is associated with exacerbation of inflammatory histopathology. During Yersinia enterocolitica infection CD4+ cells are the source of de novo TGF-β transcription in the Peyer's patches, mesenteric lymph nodes, and spleen. Correspondingly there is both antigen-specific and -independent expansion of CD4+ CD25+ Foxp3+ and TGF-β+ T-regulatory cells (T-regs) after Yersinia infection that is reduced in ovalbumin T-cell receptor-restricted OT-II mice. Functional inactivation of CD25 by anti-CD25 treatment results in more rapid death, dissemination of the bacteria to the liver and lungs, and exacerbated inflammatory histopathology, similar to what is seen during TGF-β neutralization. Altogether, these data suggest that TGF-β produced by T-regs is important in restricting bacteria during the acute phase of invasive bacterial infection of the gut. These data expand the roles of T-regs to include tempering inflammation during acute infection in addition to the well-established roles of T-regs in chronic infection, control of immune homeostasis, and autoimmune disease.

Differential Characteristics of Inflammatory Responses to Stent Implantation Between De Novo and Intrastent Restenosis Lesion in Patients With Stable Angina

Angiology ◽  
2011 ◽  
Vol 63 (2) ◽  
pp. 92-95 ◽  
Author(s):  
Hiroyuki Hikita ◽  
Shunsuke Kuroda ◽  
Naohiko Kawaguchi ◽  
Emiko Nakashima ◽  
Tatsuya Fujinami ◽  
...  
Keyword(s):  
Stent Implantation ◽  
Stable Angina ◽  
De Novo ◽  
Inflammatory Responses

scholarly journals Interaction between integrin α9β1 and vascular cell adhesion molecule-1 (VCAM-1) inhibits neutrophil apoptosis

Blood ◽  
2006 ◽  
Vol 107 (3) ◽  
pp. 1178-1183 ◽  
Author(s):  
Ewan A. Ross ◽  
Mike R. Douglas ◽  
See Heng Wong ◽  
Emma J. Ross ◽  
S. John Curnow ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
De Novo ◽  
Inflammatory Responses ◽  
Prevailing Paradigm ◽  
Screening Experiments ◽  
Induced Apoptosis ◽  
Neutrophil Survival ◽  
Cell Adhesion Molecule 1 ◽  
Kinetics Of ◽  
De Novo Protein Synthesis

AbstractAccording to the prevailing paradigm, neutrophils are short-lived cells that undergo spontaneous apoptosis within 24 hours of their release from the bone marrow. However, neutrophil survival can be significantly prolonged within inflamed tissue by cytokines, inflammatory mediators, and hypoxia. During screening experiments aimed at identifying the effect of the adhesive microenvironment on neutrophil survival, we found that VCAM-1 (CD106) was able to delay both spontaneous and Fas-induced apoptosis. VCAM-1-mediated survival was as efficient as that induced by the cytokine IFN-β and provided an additive, increased delay in apoptosis when given in combination with IFN-β. VCAM-1 delivered its antiapoptotic effect through binding the integrin α9β1. The α9β1 signaling pathway shares significant features with the IFN-β survival signaling pathway, requiring PI3 kinase, NF-κB activation, as well as de novo protein synthesis, but the kinetics of NF-κB activation by VCAM-1 were slower and more sustained compared with IFN-β. This study demonstrates a novel functional role for α9β1 in neutrophil biology and suggests that adhesive signaling pathways provide an important extrinsic checkpoint for the resolution of inflammatory responses in tissues.

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