scholarly journals Role of Interleukin-6 in Vascular Health and Disease

2021 ◽  
Vol 8 ◽  
Author(s):  
Paulina Villar-Fincheira ◽  
Fernanda Sanhueza-Olivares ◽  
Ignacio Norambuena-Soto ◽  
Nicole Cancino-Arenas ◽  
Felipe Hernandez-Vargas ◽  
...  
Keyword(s):  
Vascular System ◽  
Tissue Injury ◽  
Receptor Activation ◽  
T Cell Response ◽  
Metabolic Effects ◽  
Special Focus ◽  
Classical Pathway ◽  
Membrane Bound ◽  
Intense Training ◽  
Complex Signaling

IL-6 is usually described as a pleiotropic cytokine produced in response to tissue injury or infection. As a pro-inflammatory cytokine, IL-6 activates innate and adaptative immune responses. IL-6 is released in the innate immune response by leukocytes as well as stromal cells upon pattern recognition receptor activation. IL-6 then recruits immune cells and triggers B and T cell response. Dysregulated IL-6 activity is associated with pathologies involving chronic inflammation and autoimmunity, including atherosclerosis. However, IL-6 is also produced and released under beneficial conditions, such as exercise, where IL-6 is associated with the anti-inflammatory and metabolic effects coupled with physical adaptation to intense training. Exercise-associated IL-6 acts on adipose tissue to induce lipogenesis and on arteries to induce adaptative vascular remodeling. These divergent actions could be explained by complex signaling networks. Classical IL-6 signaling involves a membrane-bound IL-6 receptor and glycoprotein 130 (gp130), while trans-signaling relies on a soluble version of IL-6R (sIL-6R) and membrane-bound gp130. Trans-signaling, but not the classical pathway, is regulated by soluble gp130. In this review, we discuss the similarities and differences in IL-6 cytokine and myokine signaling to explain the differential and opposite effects of this protein during inflammation and exercise, with a special focus on the vascular system.

Polyphenols: Novel Signaling Pathways

2018 ◽  
Vol 24 (2) ◽  
pp. 158-170 ◽  
Author(s):  
Marie-Louise Ricketts ◽  
Bradley S. Ferguson
Keyword(s):  
Risk Factors ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Density Lipoprotein ◽  
Mechanisms Of Action ◽  
Metabolic Effects ◽  
Special Focus ◽  
In Vivo Models ◽  
Alcoholic Fatty Liver ◽  
The Metabolic Syndrome

Background: Cardiovascular disease (CVD) is currently the leading cause of death globally. The metabolic syndrome (MetS), a clustering of risk factors including hypertension, hyperglycemia, elevated low-density lipoprotein (LDL) cholesterol, reduced high-density lipoprotein (HDL) cholesterol and increased visceral adiposity, is a significant risk factor for the development of CVD. Non-alcoholic fatty liver disease (NAFLD), often referred to as the hepatic manifestation of MetS, is a constellation of progressive liver disorders closely linked to obesity, diabetes, and insulin resistance. NAFLD initially presents as relatively benign, non-progressive hepatic steatosis, but it may, in certain individuals, progress to nonalcoholic steatohepatitis, fibrosis, cirrhosis, or hepatocellular carcinoma. Currently, there are no validated treatments for NAFLD. Polyphenols are important bioactive dietary compounds and may represent a natural complementary and integrative therapy for the treatment of CVDassociated risk factors, including elevated serum cholesterol and triglyceride levels, as well as NAFLD. Understanding their molecular mechanisms of action is important in the design of future human intervention studies. Methods: Several studies utilizing in vitro and in vivo models have helped to identify underlying molecular mechanisms of action of polyphenols. Results: This review will highlight recent advances regarding the molecular actions of dietary procyanidins, with a special focus on those originating from procyanidin-rich grape seed extracts, with a focus on the signaling pathways utilized to exert beneficial metabolic effects. Conclusion: Modulation of nuclear receptor activity and histone deacetylase inhibition has been identified as underlying mechanisms contributing to procyanidin-mediated amelioration of dyslipidemia and steatosis.

Complement receptor 1 inhibitors for prevention of immune-mediated red cell destruction: potential use in transfusion therapy

Blood ◽  
2003 ◽  
Vol 101 (12) ◽  
pp. 5046-5052 ◽  
Author(s):  
Karina Yazdanbakhsh ◽  
Stanley Kang ◽  
Daniel Tamasauskas ◽  
Dorothy Sung ◽  
Andromachi Scaradavou
Keyword(s):  
Tissue Injury ◽  
Soluble Form ◽  
Complement Receptor ◽  
Classical Pathway ◽  
Human Group ◽  
Transfusion Therapy ◽  
Complement Receptor 1 ◽  
Potential Use

AbstractActivation of complement cascade via the antibody-mediated classical pathway can initiate red blood cell (RBC) destruction, causing transfusion reactions and hemolytic anemia. In the present study, we have assessed the ability of a human recombinant soluble form of complement receptor 1 (sCR1) to inhibit complement-mediated RBC destruction in vitro and in vivo. Using an in vitro alloimmune incompatibility model, sCR1 inhibited complement activation and prevented hemolysis. Following transfusion of human group O RBCs into mice lacking detectable pre-existing antibodies against the transfused RBCs, systemic coadministration of 10 mg/kg sCR1, a dose well tolerated in human subjects for prevention of tissue injury, completely inhibited the in vivo clearance of the transfused RBCs and surface C3 deposition in the first hour after transfusion, correlating with the half-life of sCR1 in the circulation. Treatment with sCR1 increased the survival of transfused human group A RBCs in the circulation of mice with pre-existing anti-A for 2 hours after transfusion by 50%, reduced intravascular hemolysis, and lowered the levels of complement deposition (C3 and C4), but not immunoglobulin G (IgG) or IgM, on the transfused cells by 100-fold. We further identified potential functional domains in CR1 that can act to limit complement-mediated RBC destruction in vitro and in vivo. Collectively, our data highlight a potential use of CR1-based inhibitors for prevention of complement-dependent immune hemolysis.

scholarly journals Extracellular Vesicles as Biological Shuttles for Targeted Therapies

2019 ◽  
Vol 20 (8) ◽  
pp. 1848 ◽  
Author(s):  
Stefania Raimondo ◽  
Gianluca Giavaresi ◽  
Aurelio Lorico ◽  
Riccardo Alessandro
Keyword(s):  
Extracellular Vesicles ◽  
Therapeutic Agents ◽  
Bioactive Molecules ◽  
Target Cells ◽  
Special Focus ◽  
Pathological Conditions ◽  
Critical Issues ◽  
Membrane Bound ◽  
And Function ◽  
Potential Use

The development of effective nanosystems for drug delivery represents a key challenge for the improvement of most current anticancer therapies. Recent progress in the understanding of structure and function of extracellular vesicles (EVs)—specialized membrane-bound nanocarriers for intercellular communication—suggests that they might also serve as optimal delivery systems of therapeutics. In addition to carrying proteins, lipids, DNA and different forms of RNAs, EVs can be engineered to deliver specific bioactive molecules to target cells. Exploitation of their molecular composition and physical properties, together with improvement in bio-techniques to modify their content are critical issues to target them to specific cells/tissues/organs. Here, we will discuss the current developments in the field of animal and plant-derived EVs toward their potential use for delivery of therapeutic agents in different pathological conditions, with a special focus on cancer.

Histaminergic contribution to the metabolic effects of neuroglucopenia

1997 ◽  
Vol 272 (6) ◽  
pp. R1918-R1924
Author(s):  
P. E. Molina ◽  
P. Williams ◽  
N. N. Abumrad
Keyword(s):  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Histamine Receptor ◽  
Receptor Activation ◽  
Hepatic Uptake ◽  
Metabolic Effects ◽  
Cortisol Response ◽  
Hormonal Responses ◽  
Hepatic Glucose ◽  
Group 1

We examined the contribution of central histamine receptor (H1 and H2) blockade to the glucoregulatory responses to intracerebroventricular 2-deoxy-D-glucose (2-DG) in conscious dogs. Intracerebroventricular 2-DG (2.5 mg.kg-1.min-1 for 15 min) increased plasma glucose (2-fold), blood lactate (4-fold), and glycerol (2-fold) levels. The rate of hepatic glucose production (Ra), determined isotopically, was increased two-fold. Significant increases over basal were also noted in plasma epinephrine, norepinephrine, insulin, glucagon, and cortisol. Pretreatment with cyproheptadine and cimetidine (100 micrograms each icv 15 min before 2-DG) attenuated the 2-DG-induced hyperglycemia by approximately 50% and delayed and attenuated the increase in glucose Ra (approximately 85% vs. 2-fold in group 1). Pretreatment with H1 and H2 antagonists inhibited the increases in epinephrine, norepinephrine, and glucagon in response to neuroglucopenia but did not affect the cortisol response. These findings suggest that some of the metabolic effects of neuroglucopenia, particularly the hyperglycemic response, the increased hepatic uptake of gluconeogenic precursors, and the enhanced glucose Ra, are partly mediated through central histaminergic receptor activation. This appears to be through effects of histaminergic activation on the autonomic and hormonal responses to central neuroglucopenia.

Crosstalk between the CX3CL1/CX3CR1 Axis and Inflammatory Signaling Pathways in Tissue Injury

2019 ◽  
Vol 20 (8) ◽  
pp. 844-854 ◽  
Author(s):  
Quan Zhuang ◽  
Jiarui Ou ◽  
Sheng Zhang ◽  
Yingzi Ming
Keyword(s):  
Signaling Pathways ◽  
Tissue Injury ◽  
Signaling Networks ◽  
Toll Like Receptor ◽  
Inflammatory Signaling ◽  
Inflammatory Cascade ◽  
Inflammatory Processes ◽  
Membrane Bound ◽  
G Protein Coupled ◽  
Receptor Cx3cr1

During inflammation, chemokines play a central role by mediating the activation of inflammatory cascade responses in tissue injury. Among more than 200 chemokines, CX3CL1 is a special chemotactic factor existing in both membrane-bound and soluble forms. Its only receptor, CX3CR1, is a member of the G protein-coupled receptor superfamily. The CX3CL1/CX3CR1 axis can affect many inflammatory processes by communicating with different inflammatory signaling pathways, such as JAK-STAT, Toll-like receptor, MAPK, AKT, NF-κB, Wnt/β-catenin, as well as others. These inflammatory networks are involved in much pathology. Determining the crosstalk between the CX3CL1/CX3CR1 axis and these inflammatory signaling pathways could contribute to solving problems in tissue injury, and the CX3CL1/CX3CR1 axis may be a better therapeutic target than inflammatory signaling pathways for preventing tissue injury due to the complexity of inflammatory signaling networks.

Cytokines regulate membrane-bound leukocyte elastase on neutrophils: a novel mechanism for effector activity

1997 ◽  
Vol 272 (3) ◽  
pp. L385-L393 ◽  
Author(s):  
C. A. Owen ◽  
M. A. Campbell ◽  
S. S. Boukedes ◽  
E. J. Campbell
Keyword(s):  
Cell Surface ◽  
Inflammatory Responses ◽  
Tissue Injury ◽  
Human Leukocyte ◽  
Tnf Alpha ◽  
Elastase Activity ◽  
Leukocyte Elastase ◽  
Necrosis Factor Alpha ◽  
Proinflammatory Mediators ◽  
Membrane Bound

Membrane-bound leukocyte elastase activity on neutrophils may have potent proinflammatory effects. Herein, we report the effects of tumor necrosis factor-alpha (TNF-alpha), platelet-activating factor (PAF), N-formyl-leucyl-methionyl-phenylalanine (fMLP), and interleukin-8 (IL-8) on membrane-bound elastase expression. TNF-alpha or PAF alone induced only approximately two- to threefold increases in membrane-bound elastase but exhibited marked dose- and time-dependent priming effects for subsequent stimulation with fMLP or IL-8 (up to 20-fold increases in membrane-bound human leukocyte elastase compared with unstimulated cells). Optimally PAF-primed and fMLP-stimulated cells expressed 1.105 +/- 0.25 (SD) x 10(-17) mol [6.65 +/- 1.51 (SD) x 10(6) molecules] membrane-bound elastase activity/cell or approximately 12% of the content of unstimulated cells. Elastase binds to the cell surface by a charge-dependent mechanism since 1) incubation of cells with cationic molecules abrogated agonist-induced upregulation of membrane-bound elastase and 2) elastase was progressively eluted from the cell surface by solutions with increasing ionic strength. Thus interactions between proinflammatory mediators strikingly upregulate membrane-bound elastase on neutrophils, which may promote inflammatory responses and/or contribute to tissue injury.

scholarly journals Identification of Proteins Likely To Be Involved in Morphogenesis, Cell Division, and Signal Transduction in Planctomycetes by Comparative Genomics

2012 ◽  
Vol 194 (23) ◽  
pp. 6419-6430 ◽  
Author(s):  
Christian Jogler ◽  
Jost Waldmann ◽  
Xiaoluo Huang ◽  
Mareike Jogler ◽  
Frank Oliver Glöckner ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Cell Division ◽  
Model Organisms ◽  
Genetic Studies ◽  
Content Type ◽  
Life Styles ◽  
Membrane Bound ◽  
Guilt By Association ◽  
Complex Signaling ◽  
Signal Transduction Systems

ABSTRACTMembers of thePlanctomycetesclade share many unusual features for bacteria. Their cytoplasm contains membrane-bound compartments, they lack peptidoglycan and FtsZ, they divide by polar budding, and they are capable of endocytosis. Planctomycete genomes have remained enigmatic, generally being quite large (up to 9 Mb), and on average, 55% of their predicted proteins are of unknown function. Importantly, proteins related to the unusual traits ofPlanctomycetesremain largely unknown. Thus, we embarked on bioinformatic analyses of these genomes in an effort to predict proteins that are likely to be involved in compartmentalization, cell division, and signal transduction. We used three complementary strategies. First, we defined thePlanctomycetescore genome and subtracted genes of well-studied model organisms. Second, we analyzed the gene content and synteny of morphogenesis and cell division genes and combined both methods using a “guilt-by-association” approach. Third, we identified signal transduction systems as well as sigma factors. These analyses provide a manageable list of candidate genes for future genetic studies and provide evidence for complex signaling in thePlanctomycetesakin to that observed for bacteria with complex life-styles, such asMyxococcus xanthus.

scholarly journals Phylogenetic evidence for the modular evolution of metazoan signalling pathways

2017 ◽  
Vol 372 (1713) ◽  
pp. 20150477 ◽  
Author(s):  
Leslie S. Babonis ◽  
Mark Q. Martindale
Keyword(s):  
Cell Signalling ◽  
Large Body ◽  
Morphological Diversity ◽  
Signalling Pathway ◽  
Signalling Pathways ◽  
Special Focus ◽  
Tissue Interactions ◽  
Modular Evolution ◽  
Membrane Bound ◽  
Evo Devo

Communication among cells was paramount to the evolutionary increase in cell type diversity and, ultimately, the origin of large body size. Across the diversity of Metazoa, there are only few conserved cell signalling pathways known to orchestrate the complex cell and tissue interactions regulating development; thus, modification to these few pathways has been responsible for generating diversity during the evolution of animals. Here, we summarize evidence for the origin and putative function of the intracellular, membrane-bound and secreted components of seven metazoan cell signalling pathways with a special focus on early branching metazoans (ctenophores, poriferans, placozoans and cnidarians) and basal unikonts (amoebozoans, fungi, filastereans and choanoflagellates). We highlight the modular incorporation of intra- and extracellular components in each signalling pathway and suggest that increases in the complexity of the extracellular matrix may have further promoted the modulation of cell signalling during metazoan evolution. Most importantly, this updated view of metazoan signalling pathways highlights the need for explicit study of canonical signalling pathway components in taxa that do not operate a complete signalling pathway. Studies like these are critical for developing a deeper understanding of the evolution of cell signalling. This article is part of the themed issue ‘Evo-devo in the genomics era, and the origins of morphological diversity’.

Sign in / Sign up

Export Citation Format

Share Document