scholarly journals Pleiotropic Functions of HDL Lead to Protection from Atherosclerosis and Other Diseases

10.5772/30054 ◽  
2012 ◽  
Author(s):  
Vassilis Zannis ◽  
Andreas Kateifides ◽  
Panagiotis Fotakis ◽  
Eleni Zanni ◽  
Dimitris Kardassis
Keyword(s):  
Pleiotropic Functions

scholarly journals IL-33 and Superantigenic Activation of Human Lung Mast Cells Induce the Release of Angiogenic and Lymphangiogenic Factors

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 145
Author(s):  
Leonardo Cristinziano ◽  
Remo Poto ◽  
Gjada Criscuolo ◽  
Anne Lise Ferrara ◽  
Maria Rosaria Galdiero ◽  
...  
Keyword(s):  
Mast Cells ◽  
Human Lung ◽  
Protein A ◽  
Protein L ◽  
Variable Regions ◽  
Prolonged Incubation ◽  
High Affinity ◽  
High Affinity Receptor ◽  
Affinity Receptor ◽  
Pleiotropic Functions

Human lung mast cells (HLMCs) express the high-affinity receptor FcεRI for IgE and are strategically located in different compartments of human lung, where they play a role in several inflammatory disorders and cancer. Immunoglobulin superantigens (e.g., protein A of Staphylococcus aureus and protein L of Peptostreptococcus magnus) bind to the variable regions of either the heavy (VH3) or light chain (κ) of IgE. IL-33 is a cytokine expressed by epithelial cells that exerts pleiotropic functions in the lung. The present study investigated whether immunoglobulin superantigens protein A and protein L and IL-33 caused the release of inflammatory (histamine), angiogenic (VEGF-A) and lymphangiogenic (VEGF-C) factors from HLMCs. The results show that protein A and protein L induced the rapid (30 min) release of preformed histamine from HLMCs. By contrast, IL-33 did not induce the release of histamine from lung mast cells. Prolonged incubation (12 h) of HLMCs with superantigens and IL-33 induced the release of VEGF-A and VEGF-C. Preincubation with IL-33 potentiated the superantigenic release of histamine, angiogenic and lymphangiogenic factors from HLMCs. Our results suggest that IL-33 might enhance the inflammatory, angiogenic and lymphangiogenic activities of lung mast cells in pulmonary disorders.

scholarly journals The Multifaced Role of STAT3 in Cancer and Its Implication for Anticancer Therapy

2021 ◽  
Vol 22 (2) ◽  
pp. 603
Author(s):  
Manlio Tolomeo ◽  
Antonio Cascio
Keyword(s):  
Tumor Promoter ◽  
Tumor Type ◽  
Signal Transducer ◽  
Suppressor Factor ◽  
Specific Tumor ◽  
Cytokine Stimulation ◽  
Pleiotropic Functions ◽  
Stat3 Mutations ◽  
Potent Tumor

Signal transducer and activator of transcription (STAT) 3 is one of the most complex regulators of transcription. Constitutive activation of STAT3 has been reported in many types of tumors and depends on mechanisms such as hyperactivation of receptors for pro-oncogenic cytokines and growth factors, loss of negative regulation, and excessive cytokine stimulation. In contrast, somatic STAT3 mutations are less frequent in cancer. Several oncogenic targets of STAT3 have been recently identified such as c-myc, c-Jun, PLK-1, Pim1/2, Bcl-2, VEGF, bFGF, and Cten, and inhibitors of STAT3 have been developed for cancer prevention and treatment. However, despite the oncogenic role of STAT3 having been widely demonstrated, an increasing amount of data indicate that STAT3 functions are multifaced and not easy to classify. In fact, the specific cellular role of STAT3 seems to be determined by the integration of multiple signals, by the oncogenic environment, and by the alternative splicing into two distinct isoforms, STAT3α and STAT3β. On the basis of these different conditions, STAT3 can act both as a potent tumor promoter or tumor suppressor factor. This implies that the therapies based on STAT3 modulators should be performed considering the pleiotropic functions of this transcription factor and tailored to the specific tumor type.

Immunofluorescent localization of the ubiquitin-activating enzyme, E1, to the nucleus and cytoskeleton

1993 ◽  
Vol 264 (1) ◽  
pp. C93-C102 ◽  
Author(s):  
J. S. Trausch ◽  
S. J. Grenfell ◽  
P. M. Handley-Gearhart ◽  
A. Ciechanover ◽  
A. L. Schwartz
Keyword(s):  
Cell Lines ◽  
Chinese Hamster ◽  
Eukaryotic Cell ◽  
Nuclear Staining ◽  
Immunofluorescent Localization ◽  
Acid Protein ◽  
Ubiquitin Conjugation ◽  
Double Label ◽  
Pleiotropic Functions ◽  
Amino Acid Protein

Ubiquitin, a 76-amino acid protein, is covalently attached to abnormal and short-lived proteins, thus marking them for ATP-dependent proteolysis in eukaryotic cells. Ubiquitin is found within the cytoplasm, nucleus, microvilli, autophagic vacuoles, and lysosomes. The ubiquitin-activating enzyme, E1, catalyzes the first step in ubiquitin conjugation. To date, very little is known about the subcellular distribution of this enzyme. We have utilized immunofluorescence and immunoblotting to examine the cellular distribution of E1 in several eukaryotic cell lines, including HeLa, smooth muscle A7r5, choriocarcinoma BeWo, Pt K1, and Chinese hamster ovary (CHO) E36. E1 was identified in both cytoplasmic and nuclear compartments in all cell lines examined. However, the relative abundance within these compartments differed markedly between the cell lines. Even within a single cell line, nuclear distribution was not uniform, and certain cells demonstrated an absence of nuclear staining. E1 resides predominantly within the nucleus in BeWo. In contrast, its distribution in CHO and Pt K1 cells is mainly cytoplasmic. Within the cytoplasm, three pools of E1 were identified by double-label immunofluorescence. The first of these colocalized with phalloidin, indicating association of E1 with actin filaments. A second cytoplasmic pool colocalized with tubulin and was predominantly perinuclear in its distribution. The third pool associated with intermediate filaments. This suggests that E1 is associated with all three components of the cytoskeleton. The distribution of E1 was unaltered in a mutant line of CHO E36 designated ts20, in which the E1 can be thermally inactivated. The variable distribution of E1 among cell lines, including its apparent cytoskeletal association, suggests pleiotropic functions of this enzyme and the ubiquitin-conjugating system.

scholarly journals Pleiotropic Functions of RB Protein in Tumor Suppression

2015 ◽  
Vol 3 (3) ◽  
Author(s):  
Naoyuki Hayashi ◽  
Chiaki Takahashi
Keyword(s):  
Tumor Suppression ◽  
Rb Protein ◽  
Pleiotropic Functions

scholarly journals Neuropeptides in modulation of Drosophila behavior: how to get a grip on their pleiotropic actions

2019 ◽  
Author(s):  
Dick R Nässel ◽  
Dennis Pauls ◽  
Wolf Huetteroth
Keyword(s):  
Expression Pattern ◽  
Internal State ◽  
Neurosecretory Cells ◽  
Higher Order ◽  
Specific Expression ◽  
Specific Expression Pattern ◽  
Pleiotropic Functions ◽  
Pleiotropic Actions ◽  
The Brain ◽  
Different Levels

Neuropeptides constitute a large and diverse class of signaling molecules that are produced by many types of neurons, neurosecretory cells, endocrines and other cells. Many neuropeptides display pleiotropic actions either as neuromodulators, co-transmitters or circulating hormones, while some play these roles concurrently. Here, we highlight pleiotropic functions of neuropeptides and different levels of neuropeptide signaling in the brain, from context-dependent orchestrating signaling by higher order neurons, to local executive modulation in specific circuits. Additionally, orchestrating neurons receive peptidergic signals from neurons conveying organismal internal state cues and relay these to executive circuits. We exemplify these levels of signaling with four neuropeptides, SIFamide, short neuropeptide F, allatostatin-A and leucokinin, each with a specific expression pattern and level of complexity in signaling.

scholarly journals A Novel Method of Immunomodulation of Endothelial cells Using Streptococcus Pyogenes and its Lysate

2020 ◽  
Author(s):  
Mark Christopher Arokiaraj ◽  
Jarad Wilson
Keyword(s):  
Cell Culture ◽  
Endothelial Cells ◽  
Coronary Artery ◽  
Streptococcus Pyogenes ◽  
Immune Modulation ◽  
Principal Component ◽  
Second Phase ◽  
Novel Method ◽  
Artery Disease ◽  
Pleiotropic Functions

AbstractBackgroundCoronary artery diseases and autoimmune disorders are common in clinical practice. In this study, a novel method of immune-modulation to modify the endothelial function was studied to modulate the features of the endothelial cells, and thereby to reduce coronary artery disease and other disorders modulated by endothelium.MethodsHUVEC cells were seeded in the cell culture, and streptococcus pyogenes were added to the cell culture, and the supernatant was studied for the secreted proteins. In the second phase, the bacterial lysate was synthesized, and the lysate was added to cell culture; and the proteins in the supernatant were studied at various time intervals.ResultsWhen streptococcus pyogenes alone was added to culture, E Cadherin, Angiostatin, EpCAM and PDGF-AB were some of the biomarkers elevated significantly. HCC1, IGFBP2 and TIMP were some of the biomarkers which showed a reduction. When the lysate was added, the cell-culture was maintained for a longer time, and it showed the synthesis of immune regulatory cytokines. Heatmap analysis showed a significant number of proteins/cytokines concerning the immune/pathways, and toll-like receptors superfamily were modified. BLC, IL 17, BMP 7, PARC, Contactin2, IL 10 Rb, NAP 2 (CXCL 7), Eotaxin 2 were maximally increased. By principal component analysis, the results observed were significant.ConclusionThere is potential for a novel method of immunomodulation of the endothelial cells, which have pleiotropic functions, using streptococcus pyogenes and its lysates.

scholarly journals Extracellular vesicle budding is inhibited by redundant regulators of TAT-5 flippase localization and phospholipid asymmetry

2018 ◽  
Vol 115 (6) ◽  
pp. E1127-E1136 ◽  
Author(s):  
Katharina B. Beer ◽  
Jennifer Rivas-Castillo ◽  
Kenneth Kuhn ◽  
Gholamreza Fazeli ◽  
Birgit Karmann ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Extracellular Vesicle ◽  
Endosomal Trafficking ◽  
Vesicle Budding ◽  
Sorting Nexins ◽  
Dnaj Protein ◽  
Membrane Budding ◽  
Pleiotropic Functions

Cells release extracellular vesicles (EVs) that mediate intercellular communication and repair damaged membranes. Despite the pleiotropic functions of EVs in vitro, their in vivo function is debated, largely because it is unclear how to induce or inhibit their formation. In particular, the mechanisms of EV release by plasma membrane budding or ectocytosis are poorly understood. We previously showed that TAT-5 phospholipid flippase activity maintains the asymmetric localization of the lipid phosphatidylethanolamine (PE) in the plasma membrane and inhibits EV budding by ectocytosis in Caenorhabditis elegans. However, no proteins that inhibit ectocytosis upstream of TAT-5 were known. Here, we identify TAT-5 regulators associated with retrograde endosomal recycling: PI3Kinase VPS-34, Beclin1 homolog BEC-1, DnaJ protein RME-8, and the uncharacterized Dopey homolog PAD-1. PI3Kinase, RME-8, and semiredundant sorting nexins are required for the plasma membrane localization of TAT-5, which is important to maintain PE asymmetry and inhibit EV release. PAD-1 does not directly regulate TAT-5 localization, but is required for the lipid flipping activity of TAT-5. PAD-1 also has roles in endosomal trafficking with the GEF-like protein MON-2, which regulates PE asymmetry and EV release redundantly with sorting nexins independent of the core retromer. Thus, in addition to uncovering redundant intracellular trafficking pathways, our study identifies additional proteins that regulate EV release. This work pinpoints TAT-5 and PE as key regulators of plasma membrane budding, further supporting the model that PE externalization drives ectocytosis.

ATF3 Pleiotropic Functions Over IPF Lung Fibroblast

2019 ◽  
Author(s):  
T. Cruz ◽  
D.M. Alvarez ◽  
J. Sembrat ◽  
J. Bullock ◽  
N. Cardenes ◽  
...  
Keyword(s):  
Lung Fibroblast ◽  
Pleiotropic Functions
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