scholarly journals 5-Lipoxygenase Pathway, Dendritic Cells, and Adaptive Immunity

2004 ◽  
Vol 2004 (2) ◽  
pp. 99-105 ◽  
Author(s):  
Harizi Hedi ◽  
Gualde Norbert
Keyword(s):  
Dendritic Cells ◽  
Adaptive Immunity ◽  
Inflammatory Cells ◽  
Lipid Mediators ◽  
G Protein Coupled Receptors ◽  
Lipoxygenase Pathway ◽  
Innate And Adaptive Immunity ◽  
Paracrine Signalling ◽  
Signalling Molecules ◽  
G Protein Coupled

5-lipoxygenase (5-LO) pathway is the major source of potent proinflammatory leukotrienes (LTs) issued from the metabolism of arachidonic acid (AA), and best known for their roles in the pathogenesis of asthma. These lipid mediators are mainly released from myeloid cells and may act as physiological autocrine and paracrine signalling molecules, and play a central role in regulating the interaction between innate and adaptive immunity. The biological actions of LTs including their immunoregulatory and proinflammatory effects are mediated through extracellular specific G-protein-coupled receptors. Despite their role in inflammatory cells, such as neutrophils and macrophages, LTs may have important effects on dendritic cells (DC)-mediated adaptive immunity. Several lines of evidence show that DC not only are important source of LTs, but also become targets of their actions by producing other lipid mediators and proinflammatory molecules. This review focuses on advances in 5-LO pathway biology, the production of LTs from DC and their role on various cells of immune system and in adaptive immunity.

scholarly journals MECHANISMS IN ENDOCRINOLOGY: An update in the genetic aetiologies of combined pituitary hormone deficiency

2016 ◽  
Vol 174 (6) ◽  
pp. R239-R247 ◽  
Author(s):  
Frederic Castinetti ◽  
Rachel Reynaud ◽  
Alexandru Saveanu ◽  
Nicolas Jullien ◽  
Marie Helene Quentien ◽  
...  
Keyword(s):  
Transcription Factors ◽  
G Protein Coupled Receptors ◽  
Hormone Deficiency ◽  
Immunoglobulin Superfamily ◽  
Pituitary Hormone ◽  
Pituitary Hormone Deficiency ◽  
Combined Pituitary Hormone Deficiency ◽  
Signalling Molecules ◽  
Genes Encoding ◽  
G Protein Coupled

Over the last 5 years, new actors involved in the pathogenesis of combined pituitary hormone deficiency in humans have been reported: they included a member of the immunoglobulin superfamily glycoprotein and ciliary G protein-coupled receptors, as well as new transcription factors and signalling molecules. New modes of inheritance for alterations of genes encoding transcription factors have also been described. Finally, actors known to be involved in a very specific phenotype (hypogonadotroph hypogonadism for instance) have been identified in a wider range of phenotypes. These data thus suggest that new mechanisms could explain the low rate of aetiological identification in this heterogeneous group of diseases. Taking into account the fact that several reviews have been published in recent years on classical aetiologies of CPHD such as mutations ofPOU1F1orPROP1, we focused the present overview on the data published in the last 5 years, to provide the reader with an updated review on this rapidly evolving field of knowledge.

scholarly journals The Prokineticins: Neuromodulators and Mediators of Inflammation and Myeloid Cell-Dependent Angiogenesis

2018 ◽  
Vol 98 (2) ◽  
pp. 1055-1082 ◽  
Author(s):  
Lucia Negri ◽  
Napoleone Ferrara
Keyword(s):  
Cancer Progression ◽  
Developmental Disorder ◽  
Tissue Injury ◽  
Myeloid Cell ◽  
Inflammatory Cells ◽  
G Protein Coupled Receptors ◽  
Mediators Of Inflammation ◽  
Motility Regulation ◽  
G Protein Coupled ◽  
Stimulating Factor

The mammalian prokineticins family comprises two conserved proteins, EG-VEGF/PROK1 and Bv8/PROK2, and their two highly related G protein-coupled receptors, PKR1 and PKR2. This signaling system has been linked to several important biological functions, including gastrointestinal tract motility, regulation of circadian rhythms, neurogenesis, angiogenesis and cancer progression, hematopoiesis, and nociception. Mutations in PKR2 or Bv8/PROK2 have been associated with Kallmann syndrome, a developmental disorder characterized by defective olfactory bulb neurogenesis, impaired development of gonadotropin-releasing hormone neurons, and infertility. Also, Bv8/PROK2 is strongly upregulated in neutrophils and other inflammatory cells in response to granulocyte-colony stimulating factor or other myeloid growth factors and functions as a pronociceptive mediator in inflamed tissues as well as a regulator of myeloid cell-dependent tumor angiogenesis. Bv8/PROK2 has been also implicated in neuropathic pain. Anti-Bv8/PROK2 antibodies or small molecule PKR inhibitors ameliorate pain arising from tissue injury and inhibit angiogenesis and inflammation associated with tumors or some autoimmune disorders.

Intracrine signaling through lipid mediators and their cognate nuclear G-protein-coupled receptors: a paradigm based on PGE2, PAF, and LPA1 receptorsThis paper is one of a selection of papers published in this Special Issue, entitled The Nucleus: A Cell Within A Cell.

2006 ◽  
Vol 84 (3-4) ◽  
pp. 377-391 ◽  
Author(s):  
Tang Zhu ◽  
Fernand Gobeil ◽  
Alejandro Vazquez-Tello ◽  
Martin Leduc ◽  
Lenka Rihakova ◽  
...  
Keyword(s):  
G Protein ◽  
Nuclear Localization ◽  
Platelet Activating Factor ◽  
Rat Hepatocytes ◽  
Lipid Mediators ◽  
G Protein Coupled Receptors ◽  
Membrane Receptors ◽  
Surface Receptors ◽  
A Cell ◽  
G Protein Coupled

Prostaglandins (PGs), platelet-activating factor (PAF), and lysophosphatidic acid (LPA) are ubiquitous lipid mediators that play important roles in inflammation, cardiovascular homeostasis, and immunity and are also known to modulate gene expression of specific pro-inflammatory genes. The mechanism of action of these lipids is thought to be primarily dependent on their specific plasma membrane receptors belonging to the superfamily of G-protein-coupled receptors (GPCR). Increasing evidence suggests the existence of a functional intracellular GPCR population. It has been proposed that immediate effects are mediated via cell surface receptors whereas long-term responses are dependent upon intracellular receptor effects. Indeed, receptors for PAF, LPA, and PGE2 (specifically EP1, EP3, and EP4) localize at the cell nucleus of cerebral microvascular endothelial cells of newborn pigs, rat hepatocytes, and cells overexpressing each receptor. Stimulation of isolated nuclei with these lipids reveals biological functions including transcriptional regulation of major genes, namely c-fos, cylooxygenase-2, and endothelial as well as inducible nitric oxide synthase. In the present review, we shall focus on the nuclear localization and signaling of GPCRs recognizing PGE2, PAF, and LPA phospholipids as ligands. Mechanisms on how nuclear PGE2, PAF, and LPA receptors activate gene transcription and nuclear localization pathways are presented. Intracrine signaling for lipid mediators uncover novel pathways to elicit their effects; accordingly, intracellular GPCRs constitute a distinctive mode of action for gene regulation.

scholarly journals Dendritic cells—the link between innate and adaptive immunity in allergy

2002 ◽  
Vol 2 (2) ◽  
pp. 93-95 ◽  
Author(s):  
Thilo Jakob ◽  
Claudia Traidl- Hoffmann ◽  
Heidrun Behrendt
Keyword(s):  
Dendritic Cells ◽  
Adaptive Immunity ◽  
Innate And Adaptive Immunity

scholarly journals Pleiotropic effects of PPAR-α – from benchside to bedside

2021 ◽  
Vol 23 (3) ◽  
pp. 439-454
Author(s):  
I. V. Shirinsky ◽  
V. S. Shirinsky
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Lipid Metabolism ◽  
Chronic Diseases ◽  
Adaptive Immunity ◽  
Biological Effects ◽  
Pleiotropic Effects ◽  
Innate And Adaptive Immunity ◽  
Glucose And Lipid Metabolism ◽  
Randomized Controlled Studies

Here we review literature data on properties of a member of nuclear hormone receptors - peroxisome proliferator-activated receptor-α. It was shown that PPARα was expressed on different cells including dendritic cells, macrophages, B- and T-cells. We discuss structure of natural and synthetic ligands of PPARa, molecular and cellular mechanisms of PPARa regulation of lipid and carbohydrate cellular metabolism. PPARa activity in hepatocytes results in decrease of intracellular concentrations of lipid acids. This leads to reduction of VLDL cholesterol, increase in HDL-cholesterol and decrease in triglycerides in plasma of patients taking PPARα agonists. Modulation of PPARa activity may change multiple biological effects of glucocorticoids (GCS) and insulin resistance. It is assumed that PPARα agonists reduce side effects of GCS and at the same time enhance their anti-inflammatory activity due to transrepression of NF-kB. We analyzed the results of several randomized studies, meta-analyses devoted to assessment of efficacy and safety of PPARa agonist fenofibrate in patients with type 2 diabetes mellitus with high risk of micro- and macrovascular events. The studies showed good safety profile of monotherapy with fibrates as well as of their combinations with statins, ezetimibe. Fibrates reduced not only cardiovascular events but also overall mortality. We present the data on the role of PPARa in control of glucose and lipid metabolism in subpopulations of innate and adaptive immunity cells. The data show that glucose and lipid metabolism play an important role in the fate of cells of innate and adaptive immunity. The metabolic state of lymphocytes has dynamic nature and depends on their functional activity. Transition from dormant cells with relatively low metabolism rate to activated and proliferating cells is accompanied with increase of metabolic demands. This transition is supported with the switch from oxidative metabolism to anaerobic glycolysis (Warburg effect) after antigen recognition by T-cells and B-cells. It was shown that granulocytes, dendritic cells and M1 macrophages were dependent on glucose metabolism during their activation while M2 macrophages were dependent on fatty acids oxidation. In contrast with lymphocytes, activated myeloid cells do not proliferate well but still have increased glycolysis which is necessary for their effector function. It is stressed that modulation of immune cells metabolism via PPARα gives new opportunities to modulate intensity and duration of immune responses in chronic diseases. We analyze studies performed on animal models of some chronic diseases, human patients with rheumatoid arthritis and different phenotypes of osteoarthritis. Most of the studies showed clinical efficacy and pleiotropic effects of PPARα agonists: antiinflammatory, immunomodulating and lipid modulating, primarily reduction of triglycerides and increase in HDL-C. The presented literature data suggest efficacy of PPARα agonists against individual components of polypathies. This could reduce risk of polypharmacy and reduce direct treatment costs. It is not unlikely that the use of PPARα agonists in a patient with multimorbidity could prevent acquiring a new disease. These are merely suggestions and much effort and time is required to perform large-scale randomized controlled studies evaluating new indications for the use of PPARa agonists.

scholarly journals Investigation of fascin1, a marker of mature dendritic cells, reveals a New role for IL-6 signaling in chemotaxis

2020 ◽  
Author(s):  
Fumio Matsumura ◽  
Robin Polz ◽  
Sukhwinder Singh ◽  
Jürgen Scheller ◽  
Shigeko Yamashiro
Keyword(s):  
Dendritic Cells ◽  
Lymph Nodes ◽  
G Protein ◽  
Molecular Mechanism ◽  
Adaptive Immunity ◽  
Initial Step ◽  
Regulatory Pathway ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

AbstractMigration of mature dendritic cells (DCs) to lymph nodes is critical for the initiation of adaptive immunity. While CCR7, a a G-protein-coupled receptor for CCL19/21 chemokines, is known to be essential for chemotaxis of mature DCs, the molecular mechanism linking inflammation to chemotaxis remains unclear. We previously demonstrated that fascin1, an actin-bundling protein, increases chemotaxis of mature DCs. In this paper we showed that fascin1 enhanced Interleukin (IL)-6 secretion and signaling. Furthermore, we demonstrated that IL-6 signaling is required for chemotaxis. Blockage of IL-6 signaling in WT DCs with an anti-IL-6 receptorα (IL-6Rα) antibody inhibited chemotaxis toward CCL19. Likewise, knockout (KO) of IL-6Rα inhibited chemotaxis of BMDCs. The addition of soluble IL-6Rα and IL-6 rescued chemotaxis of IL-6Rα KO BMDCs, underscoring the role of IL-6 signaling in chemotaxis. We found that IL-6 signaling is required for internalization of CCR7, the initial step of CCR7 recycling. CCR7 recycling is known to be essential for CCR7-mediated chemotaxis, explaining why IL-6 signaling is needed for chemotaxis of mature DCs. Our results have identified IL-6 signaling as a new regulatory pathway for CCR7/CCL19-mediated chemotaxis, and suggest that rapid migration of mature DCs to lymph nodes depends on inflammation-associated IL-6 signaling.

scholarly journals The complex role of Prostaglandin E2-EP receptor signaling in wound healing

2020 ◽  
Author(s):  
Kristy E. Gilman ◽  
Kirsten H. Limesand
Keyword(s):  
Wound Healing ◽  
G Protein ◽  
Lipid Mediators ◽  
G Protein Coupled Receptors ◽  
Prostaglandin E ◽  
Receptor Signaling ◽  
Wound Healing Response ◽  
Ep Receptor ◽  
G Protein Coupled

Prostaglandins are critical lipid mediators involved in the wound healing response, with prostaglandin E2 (PGE2) being the most complex and exhibiting the most diverse physiological outputs. PGE2 signals via four G-protein coupled receptors, termed EP-receptors 1-4, that induce distinct signaling pathways upon activation and lead to an array of different outputs. Recent studies examining the role of PGE2 and EP receptor signaling in wound healing following various forms of tissue damage are discussed in this review.

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