Mast Cell-Related Diseases: Genetics, Signaling Pathways, and Novel Therapies

2003 ◽  
pp. 307-355 ◽  
Author(s):  
Michael A. Beaven ◽  
Thomas R. Hundley
Keyword(s):  
Mast Cell ◽  
Signaling Pathways ◽  
Novel Therapies

scholarly journals Tim-3 enhances FcεRI-proximal signaling to modulate mast cell activation

2015 ◽  
Vol 212 (13) ◽  
pp. 2289-2304 ◽  
Author(s):  
Binh L. Phong ◽  
Lyndsay Avery ◽  
Tina L. Sumpter ◽  
Jacob V. Gorman ◽  
Simon C. Watkins ◽  
...  
Keyword(s):  
T Cells ◽  
Mast Cell ◽  
Signaling Pathways ◽  
Cell Activation ◽  
Molecular Mechanisms ◽  
Late Phase ◽  
Cell Types ◽  
Mast Cell Activation ◽  
Positive Role ◽  
Ample Evidence

T cell (or transmembrane) immunoglobulin and mucin domain protein 3 (Tim-3) has attracted significant attention as a novel immune checkpoint receptor (ICR) on chronically stimulated, often dysfunctional, T cells. Antibodies to Tim-3 can enhance antiviral and antitumor immune responses. Tim-3 is also constitutively expressed by mast cells, NK cells and specific subsets of macrophages and dendritic cells. There is ample evidence for a positive role for Tim-3 in these latter cell types, which is at odds with the model of Tim-3 as an inhibitory molecule on T cells. At this point, little is known about the molecular mechanisms by which Tim-3 regulates the function of T cells or other cell types. We have focused on defining the effects of Tim-3 ligation on mast cell activation, as these cells constitutively express Tim-3 and are activated through an ITAM-containing receptor for IgE (FcεRI), using signaling pathways analogous to those in T cells. Using a variety of gain- and loss-of-function approaches, we find that Tim-3 acts at a receptor-proximal point to enhance Lyn kinase-dependent signaling pathways that modulate both immediate-phase degranulation and late-phase cytokine production downstream of FcεRI ligation.

Novel Therapies Targeting Signaling Pathways in Lung Cancer

2006 ◽  
Vol 16 (4) ◽  
pp. 379-396 ◽  
Author(s):  
Adam Yagui-Beltrán ◽  
Biao He ◽  
Dan Raz ◽  
Jae Kim ◽  
David M. Jablons
Keyword(s):  
Lung Cancer ◽  
Signaling Pathways ◽  
Novel Therapies

scholarly journals Targeting Signaling Pathways in Inflammatory Breast Cancer

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2479
Author(s):  
Xiaoping Wang ◽  
Takashi Semba ◽  
Lan Thi Hanh Phi ◽  
Sudpreeda Chainitikun ◽  
Toshiaki Iwase ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Signaling Pathways ◽  
Inflammatory Breast Cancer ◽  
Poor Prognosis ◽  
High Rate ◽  
Novel Therapies ◽  
Biological Functions ◽  
Novel Targets ◽  
Preclinical And Clinical Studies ◽  
Related Mortality

Inflammatory breast cancer (IBC), although rare, is the most aggressive type of breast cancer. Only 2–4% of breast cancer cases are classified as IBC, but—owing to its high rate of metastasis and poor prognosis—8% to 10% of breast cancer-related mortality occur in patients with IBC. Currently, IBC-specific targeted therapies are not available, and there is a critical need for novel therapies derived via understanding novel targets. In this review, we summarize the biological functions of critical signaling pathways in the progression of IBC and the preclinical and clinical studies of targeting these pathways in IBC. We also discuss studies of crosstalk between several signaling pathways and the IBC tumor microenvironment.

scholarly journals Ethanol Extract of Sesamum indicum Linn. Inhibits FcεRI-Mediated Allergic Reaction via Regulation of Lyn/Syk and Fyn Signaling Pathways in Rat Basophilic Leukemic RBL-2H3 Mast Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Hyun Ju Do ◽  
Tae Woo Oh ◽  
Kwang-Il Park
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Signaling Pathways ◽  
Inflammatory Mediators ◽  
Cell Activation ◽  
Immunoglobulin E ◽  
Sesamum Indicum ◽  
Mast Cell Activation ◽  
Allergic Reactions ◽  
Potent Effect

This study is aimed at determining whether Sesamum indicum Linn. beneficially influences FcεRI-mediated allergic reactions in RBL-2H3 mast cells; it is also aimed at further investigating Lyn/Fyn and Syk signaling pathways. To examine the antiallergic effect of Sesamum indicum Linn. extract (SIE), we treated antigen/immunoglobulin E- (IgE-) sensitized mast cells with extracts of various concentrations. We examined the degranulation release and concentrations of inflammatory mediators. Additionally, the expressions of genes involved in the FcεRI and arachidonate signaling pathways were examined. SIE inhibited the degranulation and secretion of inflammatory mediators in antigen/IgE-sensitized mast cells. SIE reduced the expressions of FcεRI signaling-related genes, such as Syk, Lyn, and Fyn, and the phosphorylation of extracellular signal-regulated kinase in antigen/IgE-sensitized mast cells. Additionally, in late allergic responses, SIE reduced PGD2 release and COX-2 and cPLA2 phosphorylation expression in FcεRI-mediated mast cell activation. Lastly, 250–500 mg/kg SIE significantly attenuated the Ag/IgE-induced passive cutaneous anaphylaxis (PCA) reaction in mice. The potent effect of SIE on RBL-2H3 mast cell activation indicates that the extract could potentially be used as a novel inhibitor against allergic reactions.

scholarly journals Mast Cell Chemotaxis – Chemoattractants and Signaling Pathways

2012 ◽  
Vol 3 ◽  
Author(s):  
Ivana Halova ◽  
Lubica Draberova ◽  
Petr Draber
Keyword(s):  
Mast Cell ◽  
Signaling Pathways ◽  
Cell Chemotaxis

scholarly journals Vascular Anomalies Caused by Abnormal Signaling within Endothelial Cells: Targets for Novel Therapies

2017 ◽  
Vol 34 (03) ◽  
pp. 233-238 ◽  
Author(s):  
Ha-Long Nguyen ◽  
Laurence Boon ◽  
Miikka Vikkula
Keyword(s):  
Signaling Pathways ◽  
Intracellular Signaling ◽  
Vascular Anomalies ◽  
Paradigm Change ◽  
Novel Therapies ◽  
Endothelial Cell Dysfunction ◽  
Cell Dysfunction ◽  
The Past ◽  
Intracellular Signaling Pathways ◽  
Downstream Effects

AbstractVascular anomalies arise as a consequence of improper development and maintenance of the vasculature. Our knowledge on the pathophysiological bases of vascular anomalies has skyrocketed during the past 5 years. It is becoming clear that common intracellular signaling pathways are often activated by mutations, causing endothelial cell dysfunction. These mutations cause hyperactivation of two major intracellular signaling pathways that may be controlled by inhibitors developed for cancer treatment. Although we do not know yet all the downstream effects, it has become evident that normalization of the abnormal signaling is an interesting target for therapy. This is a major paradigm change, as developmental malformations were considered to be inert to any molecular treatment.

scholarly journals FcεRI-mediated mast cell migration: Signaling pathways and dependence on cytosolic free Ca2+ concentration

2009 ◽  
Vol 21 (11) ◽  
pp. 1698-1705 ◽  
Author(s):  
In Duk Jung ◽  
Hyun-Sil Lee ◽  
Hoi Young Lee ◽  
Oksoon Hong Choi
Keyword(s):  
Mast Cell ◽  
Cell Migration ◽  
Signaling Pathways

scholarly journals Molecular Mechanisms of Mast Cell Activation by Cholesterol-Dependent Cytolysins

2021 ◽  
Vol 12 ◽  
Author(s):  
Lubica Draberova ◽  
Magda Tumova ◽  
Petr Draber
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Signaling Pathways ◽  
Inflammatory Mediators ◽  
Pore Formation ◽  
Cell Activation ◽  
Molecular Mechanisms ◽  
Biologically Active ◽  
Mast Cell Activation ◽  
Concentration Changes

Mast cells are potent immune sensors of the tissue microenvironment. Within seconds of activation, they release various preformed biologically active products and initiate the process of de novo synthesis of cytokines, chemokines, and other inflammatory mediators. This process is regulated at multiple levels. Besides the extensively studied IgE and IgG receptors, toll-like receptors, MRGPR, and other protein receptor signaling pathways, there is a critical activation pathway based on cholesterol-dependent, pore-forming cytolytic exotoxins produced by Gram-positive bacterial pathogens. This pathway is initiated by binding the exotoxins to the cholesterol-rich membrane, followed by their dimerization, multimerization, pre-pore formation, and pore formation. At low sublytic concentrations, the exotoxins induce mast cell activation, including degranulation, intracellular calcium concentration changes, and transcriptional activation, resulting in production of cytokines and other inflammatory mediators. Higher toxin concentrations lead to cell death. Similar activation events are observed when mast cells are exposed to sublytic concentrations of saponins or some other compounds interfering with the membrane integrity. We review the molecular mechanisms of mast cell activation by pore-forming bacterial exotoxins, and other compounds inducing cholesterol-dependent plasma membrane perturbations. We discuss the importance of these signaling pathways in innate and acquired immunity.

Cornuside inhibits mast cell-mediated allergic response by down-regulating MAPK and NF-κB signaling pathways

2016 ◽  
Vol 473 (2) ◽  
pp. 408-414 ◽  
Author(s):  
Liangchang Li ◽  
Guangyu Jin ◽  
Jingzhi Jiang ◽  
Mingyu Zheng ◽  
Yan Jin ◽  
...  
Keyword(s):  
Mast Cell ◽  
Signaling Pathways ◽  
Allergic Response

scholarly journals A Retrospective on Nuclear Receptor Regulation of Inflammation: Lessons from GR and PPARs

PPAR Research ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Min-Dian Li ◽  
Xiaoyong Yang
Keyword(s):  
Glucocorticoid Receptor ◽  
Signaling Pathways ◽  
Nuclear Receptors ◽  
Nuclear Receptor ◽  
Receptor Regulation ◽  
Peroxisome Proliferator ◽  
Novel Therapies ◽  
Nuclear Receptor Superfamily ◽  
Founding Member ◽  
Peroxisome Proliferator Activated Receptors

Members of the nuclear receptor superfamily have vital roles in regulating immunity and inflammation. The founding member, glucocorticoid receptor (GR), is the prototype to demonstrate immunomodulation via transrepression of the AP-1 and NF-κB signaling pathways. Peroxisome proliferator-activated receptors (PPARs) have emerged as key regulators of inflammation. This review examines the history and current advances in nuclear receptor regulation of inflammation by the crosstalk with AP-1 and NF-κB signaling, focusing on the roles of GR and PPARs. A better understanding of the molecular mechanism by which nuclear receptors inhibit proinflammatory signaling pathways will enable novel therapies to treat chronic inflammation.

Sign in / Sign up

Export Citation Format

Share Document