scholarly journals Adipose Tissue-Derived Mesenchymal Stem Cell Modulates the Immune Response of Allergic Rhinitis in a Rat Model

2019 ◽  
Vol 20 (4) ◽  
pp. 873 ◽  
Author(s):  
Nesrine Ebrahim ◽  
Yasser Mandour ◽  
Ayman Farid ◽  
Ebtesam Nafie ◽  
Amira Mohamed ◽  
...  
Keyword(s):  
Allergic Rhinitis ◽  
Adipose Tissue ◽  
Rat Model ◽  
Transforming Growth Factor ◽  
Immunoglobulin E ◽  
Physiological Saline ◽  
Transforming Growth Factor Β ◽  
Underlying Mechanism ◽  
Albino Rats ◽  
Microscopical Examination

This study was designed to investigate the potential effects and underlying mechanism of adipose tissue-derived mesenchymal stem cells (MSCs) on allergic inflammation compared to Montelukast as an antileukotriene drug in a rat model of allergic rhinitis (AR). The effect of MSCs was evaluated in albino rats that were randomly divided into four (control, AR, AR + Montelukast, and AR + MSCs) groups. Rats of AR group were sensitized by ovalbumin (OVA) and then challenged with daily nasal drops of OVA diluted in sterile physiological saline (50 μL/nostril, 100 mg/mL, 10% OVA) from day 15 to day 21 of treatment with/without Montelukast (1 h before each challenge) or MSCs I/P injection (1 × 106 MCSs; weekly for three constitutive weeks). Both Montelukast and MSCs treatment started from day 15 of the experiment. At the end of the 5th week, blood samples were collected from all rats for immunological assays, histological, and molecular biology examinations. Both oral Montelukast and intraperitoneal injection of MSCs significantly reduced allergic symptoms and OVA-specific immunoglobulin E (IgE), IgG1, IgG2a and histamine as well as increasing prostaglandin E2 (PGE2). Further analysis revealed that induction of nasal innate cytokines, such as interleukin (IL)-4 and TNF-α; and chemokines, such as CCL11 and vascular cell adhesion molecule-1 (VCAM-1), were suppressed; and transforming growth factor-β (TGF-β) was up-regulated in Montelukast and MSCs-treated groups with superior effect to MSCs, which explained their underlying mechanism. In addition, the adipose tissue-derived MSCs-treated group had more restoring effects on nasal mucosa structure demonstrated by electron microscopical examination.

Allergen immunotherapy: definition, indications, and reactions

2019 ◽  
Vol 40 (6) ◽  
pp. 369-371 ◽  
Author(s):  
Dawn K. Lei ◽  
Carol Saltoun
Keyword(s):  
Allergic Rhinitis ◽  
Allergen Immunotherapy ◽  
Transforming Growth Factor ◽  
Immunoglobulin E ◽  
Symptom Control ◽  
Transforming Growth Factor Β ◽  
Interleukin 10 ◽  
Tissue Level ◽  
Type I ◽  
Disease Modifying Therapy

Specific allergen immunotherapy is the administration of increasing amounts of specific allergens to which the patient has type I immediate hypersensitivity. It is a disease-modifying therapy, indicated for the treatment of allergic rhinitis, allergic conjunctivitis, allergic asthma, and Hymenoptera hypersensitivity. Specific immunoglobulin E (IgE) antibodies for appropriate allergens for immunotherapy must be documented. Indications for allergen immunotherapy include (1) inadequate symptom control despite pharmacotherapy and avoidance measures; (2) a desire to reduce the morbidity from allergic rhinitis and/or asthma, or reduce the risk of anaphylaxis from a future insect sting; (3) when the patient experiences undesirable adverse effects from pharmacotherapy; and (4) when avoidance is not possible. Several studies reported that immunotherapy in allergic rhinitis seems to prevent the development of new allergic sensitizations and/or new onset asthma. Humoral-, cellular-, and tissue-level changes occur with allergen immunotherapy, including induction of allergen-specific regulatory T and B cells, interleukin 10, and transforming growth factor β production; suppression of T-helper type 2 cell proliferation; large increases in anti-allergen IgG4 antibodies; and reduction in basophil, mast cell, and eosinophil mediator release. Allergen immunotherapy can be administered either subcutaneously in the physician's office or sublingually by the patient at home. The use of immunotherapy in food allergy is still under investigation.

GHSR deficiency exacerbates cardiac fibrosis: role in macrophage inflammasome activation and myofibroblast differentiation

2019 ◽  
Vol 116 (13) ◽  
pp. 2091-2102 ◽  
Author(s):  
Mo Wang ◽  
Lei Qian ◽  
Jing Li ◽  
Hao Ming ◽  
Li Fang ◽  
...  
Keyword(s):  
Cardiac Fibrosis ◽  
Transforming Growth Factor ◽  
Cardiac Fibroblasts ◽  
Cardiovascular Effects ◽  
Transforming Growth Factor Β ◽  
Underlying Mechanism ◽  
Marker Genes ◽  
Inflammasome Activation ◽  
Growth Hormone Secretagogue Receptor ◽  
Growth Hormone Secretagogue

Abstract Aims Sustained activation of β-adrenergic signalling induces cardiac fibrosis, which marks progression to heart failure. GHSR (growth hormone secretagogue receptor) is the receptor for ghrelin, which is an orexigenic gastric hormone with newly defined cardiovascular effects. The present study determined the effects of GHSR deficiency in a mouse model of isoproterenol (ISO)-induced cardiac fibrosis and examined the underlying mechanism. Methods and results Histochemical studies showed that GHSR deficiency exacerbated cardiac fibrosis. Quantitative RT–PCR, western blotting, and immunofluorescence staining demonstrated that cardiac fibroblasts isolated from GHSR−/− mice exhibited increased expression of marker genes for myofibroblast trans-differentiation (α-SMA, SM22, and calponin) upon transforming growth factor-β treatment compared to wild-type mice. RNA-sequencing of heart transcriptomes revealed that differentially expressed genes in GHSR−/− hearts were enriched in such biological processes as extracellular matrix organization, inflammatory response, lipid metabolism, cell cycle, migration, and adhesion. Particularly, GHSR deficiency increased Wnt/β-catenin pathway activation in ISO-induced myocardial fibrosis. In addition, loss of GHSR in macrophages instigated inflammasome activation with increased cleavage and release of interleukin-18. Conclusion These results for the first time demonstrated that GHSR deficiency aggravated ISO-induced cardiac fibrosis, suggesting that GHSR was a potential target for the intervention of cardiac fibrosis.

scholarly journals Activin receptor-like kinase-2 inhibits activin signaling by blocking the binding of activin to its type II receptor

2007 ◽  
Vol 195 (1) ◽  
pp. 95-103 ◽  
Author(s):  
Nina Renlund ◽  
Francis H O’Neill ◽  
LiHua Zhang ◽  
Yisrael Sidis ◽  
Jose Teixeira
Keyword(s):  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Underlying Mechanism ◽  
Luciferase Reporter ◽  
Type I ◽  
Type Ii ◽  
Activin Receptor ◽  
Activin Signaling ◽  
Endogenous Expression ◽  
Receptor Like Kinase

Activin receptor-like kinase-2 (Alk2) has been shown to be a promiscuous type I receptor for the transforming growth factor β (TGFβ) family of growth and differentiation factors, such as activin, bone morphogenetic proteins, and Müllerian inhibiting substance (MIS). We have studied the putative role of Alk2 in activin signaling using MA-10 cells, a mouse transformed Leydig cell line, in which endogenous expression of cytochrome P450 c17 hydroxylase/C17–20 lyase mRNA is inhibited by both MIS and activin A. Overexpression of Alk2 in MA-10 cells inhibited the activation of the activin-responsive CAGA-luciferase reporter and, conversely, transfection of siRNA for Alk2 increased the response. In contrast, overexpression of the MIS type II receptor in MA-10 cells increased the activin-mediated induction of CAGA-luciferase approximately fivefold, which we hypothesized occurs by MIS type II receptor sequestering endogenous Alk2. Binding experiments with 125I-labeled activin show that the underlying mechanism of Alk2-mediated inhibition of activin signaling involves Alk2 blocking the access of activin to its type II receptor, which we show can bind Alk2 in the absence of ligand. These results show that the complement of other type I receptors in addition to the ligand-specific type I receptor can provide an important mechanism for modulating cell-specific responses to members of the TGFβ family.

scholarly journals Ribozyme Oligonucleotides Against Transforming Growth Factor-β Inhibited Neointimal Formation After Vascular Injury in Rat Model

Circulation ◽  
2000 ◽  
Vol 102 (11) ◽  
pp. 1308-1314 ◽  
Author(s):  
Kei Yamamoto ◽  
Ryuichi Morishita ◽  
Naruya Tomita ◽  
Takashi Shimozato ◽  
Hironori Nakagami ◽  
...  
Keyword(s):  
Growth Factor ◽  
Vascular Injury ◽  
Rat Model ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Neointimal Formation

scholarly journals Identification of a mesenchymal progenitor cell hierarchy in adipose tissue

Science ◽  
2019 ◽  
Vol 364 (6438) ◽  
pp. eaav2501 ◽  
Author(s):  
David Merrick ◽  
Alexander Sakers ◽  
Zhazira Irgebay ◽  
Chihiro Okada ◽  
Catherine Calvert ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Progenitor Cells ◽  
Transforming Growth Factor ◽  
De Novo ◽  
Mesenchymal Cell ◽  
Transforming Growth Factor Β ◽  
Cell Types ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Dipeptidyl Peptidase 4

Metabolic health depends on the capacity of adipose tissue progenitor cells to undergo de novo adipogenesis. The cellular hierarchy and mechanisms governing adipocyte progenitor differentiation are incompletely understood. Through single-cell RNA sequence analyses, we show that the lineage hierarchy of adipocyte progenitors consists of distinct mesenchymal cell types that are present in both mouse and human adipose tissues. Cells marked by dipeptidyl peptidase–4 (DPP4)/CD26 expression are highly proliferative, multipotent progenitors. During the development of subcutaneous adipose tissue in mice, these progenitor cells give rise to intercellular adhesion molecule–1 (ICAM1)/CD54–expressing (CD54+) committed preadipocytes and a related adipogenic cell population marked by Clec11a and F3/CD142 expression. Transforming growth factor–β maintains DPP4+ cell identity and inhibits adipogenic commitment of DPP4+ and CD142+ cells. Notably, DPP4+ progenitors reside in the reticular interstitium, a recently appreciated fluid-filled space within and between tissues, including adipose depots.

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