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1.
Allergol Immunopathol (Madr) ; 52(4): 53-59, 2024.
Article in English | MEDLINE | ID: mdl-38970265

ABSTRACT

BACKGROUND: Pulmonary fibrosis is a pathological hallmark of lung injury. It is an aggressive disease that replaces normal lung parenchyma by fibrotic tissue. The transforming growth factor-beta-mothers against decapentaplegic homolog 3 (TGF-ß1-Smad3) signaling pathway plays a key role in regulating lung fibrosis. Decorin (DCN), a small leucine-rich proteoglycan, has a modulatory effect on the immune system by reversibly binding with TGF-ß and reducing its bioavailability. Mesenchymal stem cell (MSC) therapy is a new strategy that has an immune-modulatory capacity. OBJECTIVE: The aim of this study was to introduce a new therapeutic approach to harness remodeling in injured lung. MATERIAL AND METHODS: Bone marrow MSCs were isolated and transduced by decorin gene. Lung injury was induced by bleomycin and mice were treated with MSCs, MSCs-decorin, and decorin. Then, oxidative stress biomarkers, remodeling biomarkers, bronchoalveolar lavage cells, and histopathology study were conducted. RESULTS: Reduced catalase and superoxide dismutase increased due to treatments. Elevated malondialdehyde, hydroxyproline, TGF-ß levels, and polymorphonuclear cells count decreased in the treated groups. Additionally, the histopathology of lung tissues showed controlled inflammation and fibrosis. CONCLUSION: Transfected decorin gene to MSCs and used cell therapy could control remodeling and bleomycin-induced lung injury.


Subject(s)
Bleomycin , Decorin , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Pulmonary Fibrosis , Decorin/genetics , Decorin/metabolism , Animals , Mice , Pulmonary Fibrosis/immunology , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/therapy , Lung Injury/chemically induced , Lung Injury/therapy , Lung Injury/immunology , Lung Injury/genetics , Transduction, Genetic , Oxidative Stress , Cells, Cultured , Disease Models, Animal , Male , Humans
2.
Allergol Immunopathol (Madr) ; 51(2): 45-51, 2023.
Article in English | MEDLINE | ID: mdl-36916087

ABSTRACT

Asthma is an important pulmonary disease associated with T helper lymphocyte (Th)2 dominant immune response, which can initiate allergic and inflammatory reactions. Interleukin (IL)-10 is the main immune suppressor cytokine, and mesenchymal stem cells (MSCs) have an immune-modulatory potential that can be transduced with the expression of the IL-10 gene to control pathophysiology of allergic asthma. Bone marrow's MSCs were isolated and transduced with the expression vector that contains the expressible IL-10 gene. Then, allergic asthma mouse model was produced and treated with manipulated MSCs. Methacholine challenge test; measurement of IL-4, IL-5, IL-8, IL-13, IL-25, and IL-33; and total and ovalbumin (OVA)-specific immunoglobulin (Ig)E levels were done. Hyperplasia of the goblet cell, secretion of mucus, and peribronchiolar and perivascular eosinophilic inflammation were evaluated in lung pathological sections. IL-25, IL-33, and total IgE levels; AHR; eosinophilic inflammation; hyperplasia of the goblet cell; and secretion of mucus could be controlled in M, MV, and MV-10 groups, and the control in the MV-10 group was strong compared to M and MV groups. MSCs have immune-modulatory capacity that can control allergic asthma pathophysiology, and this effect can be strengthened and reinforced by the expression of IL-10 gene.


Subject(s)
Asthma , Eosinophilia , Mesenchymal Stem Cells , Animals , Mice , Asthma/genetics , Asthma/therapy , Bronchoalveolar Lavage Fluid , Cytokines , Disease Models, Animal , Hyperplasia/pathology , Immunoglobulin E , Inflammation , Interleukin-10/genetics , Interleukin-33 , Lung/pathology , Mice, Inbred BALB C , Ovalbumin
3.
Allergol. immunopatol ; 51(2): 45-51, 01 mar. 2023. ilus, graf
Article in English | IBECS | ID: ibc-216797

ABSTRACT

Asthma is an important pulmonary disease associated with T helper lymphocyte (Th)2 dominant immune response, which can initiate allergic and inflammatory reactions. Interleukin (IL)-10 is the main immune suppressor cytokine, and mesenchymal stem cells (MSCs) have an immune-modulatory potential that can be transduced with the expression of the IL-10 gene to control pathophysiology of allergic asthma. Bone marrow’s MSCs were isolated and transduced with the expression vector that contains the expressible IL-10 gene. Then, allergic asthma mouse model was produced and treated with manipulated MSCs. Methacholine challenge test; measurement of IL-4, IL-5, IL-8, IL-13, IL-25, and IL-33; and total and ovalbumin (OVA)-specific immunoglobulin (Ig)E levels were done. Hyperplasia of the goblet cell, secretion of mucus, and peribronchiolar and perivascular eosinophilic inflammation were evaluated in lung pathological sections. IL-25, IL-33, and total IgE levels; AHR; eosinophilic inflammation; hyperplasia of the goblet cell; and secretion of mucus could be controlled in M, MV, and MV-10 groups, and the control in the MV-10 group was strong compared to M and MV groups. MSCs have immune-modulatory capacity that can control allergic asthma pathophysiology, and this effect can be strengthened and reinforced by the expression of IL-10 gene (AU)


Subject(s)
Animals , Male , Mice , Cell- and Tissue-Based Therapy , Genetic Therapy , Asthma/therapy , Hypersensitivity/therapy , Interleukin-10 , Mesenchymal Stem Cells , Disease Models, Animal , Mice, Inbred BALB C , Cells, Cultured , Transduction, Genetic
4.
J Investig Med ; 71(2): 71-80, 2023 02.
Article in English | MEDLINE | ID: mdl-36647329

ABSTRACT

The pandemic of COVID-19 in worldwide causes recent millions of morbidity and mortality in all countries and is the most important challenge in the world in recent years. Coronavirus is a single-stranded RNA virus and infection with COVID-19 leads to acute respiratory distress syndrome, lung inflammation, cytokine storm, and death. The other complications include endothelial dysfunction, activation of coagulation, thromboembolic events, and vascular disease. Cardiovascular complications such as myocardial and stroke ischemia, pulmonary thromboembolism, systemic arterial, and deep vein thrombosis were reported. In this review, we presented immuno-pathological mechanisms and the effects of COVID-19 on the cardiovascular system, heart, vessels, coagulation system, and molecular glance of immuno-inflammation to the COVID-19's pathology on the cardiovascular system.


Subject(s)
COVID-19 , Cardiovascular Diseases , Thromboembolism , Humans , COVID-19/complications , Cardiovascular Diseases/complications , SARS-CoV-2 , Thromboembolism/etiology , Inflammation/complications
5.
Allergol Immunopathol (Madr) ; 50(6): 71-75, 2022.
Article in English | MEDLINE | ID: mdl-36335448

ABSTRACT

Allergic rhinitis and asthma are the main airway diseases with a higher prevalence. Eosinophilic inflammation, airway hyperresponsiveness, mucus hypersecretion, and reversible airflow obstruction are immunopathogenesis symptoms of rhinitis and asthma. Crotonic acid has bio-activity on the inflammation, and gluconic acid as chelator may protect crotonic acid activity in airway and together may control allergic rhinitis and asthma.Allergic rhinitis and asthma mice models were treated with crotonic and gluconic acids. The total IgE, histamine, IL-4, IL-5, and IL-13 levels were measured. In lung tissues, goblet cell hyperplasia, mucus hypersecretion, and inflammation were evaluated.The level of IL-5, goblet cell hyperplasia, and perivascular and peribronchial inflammation were controlled by crotonic acid in asthma and allergic rhinitis groups. But, total IgE, hista-mine, IL-4, and IL-13 levels, and mucus hypersecretion had no significant changes between treated and nontreated asthma and rhinitis groups.


Subject(s)
Asthma , Rhinitis, Allergic , Rhinitis , Mice , Animals , Interleukin-13 , Interleukin-4 , Crotonates/therapeutic use , Amides/therapeutic use , Hyperplasia , Interleukin-5 , Asthma/drug therapy , Asthma/pathology , Rhinitis, Allergic/drug therapy , Immunoglobulin E , Inflammation , Anti-Inflammatory Agents/therapeutic use , Disease Models, Animal , Cytokines , Bronchoalveolar Lavage Fluid
6.
Allergol Immunopathol (Madr) ; 50(3): 93-100, 2022.
Article in English | MEDLINE | ID: mdl-35527661

ABSTRACT

BACKGROUND: Asthma is a lung disease that has influenced more than 350 million people worldwide. Airway smooth muscle (ASM) spasm leads to airway hyperresponsiveness (AHR) and bronchial obstruction, which are clinical manifestations of an asthma attack. Botulinum toxin (BTX) is a bacteria toxin that acts as muscle relaxant and may have therapeutic effects on AHR and asthma. OBJECTIVE: In this study, the effect of BTX on AHR and related gene expressions was evaluated. MATERIAL AND METHODS: An asthma mice model was developed which was treated with BTX in two ways: intranasally (IN) and via nebulization (N) (0.01, 0.1, and 1 U/mL and 10 U/mL, respectively) on days 25, 27 and 29. AHR was evaluated on days 24, 26, 28, and 30, and gene expressions were evaluated for TrkA, TrkB, M1-M5, α7nAChR, TNF-α, and extracellular signal-regulated kinase 2 (ERK2) proteins. For histopathology of the lungs, perivascular and peribronchial inflammation, production of mucus, and goblet cell hyperplasia were studied. RESULTS: On day 24, treatment with BTX (for all doses) had no significant effect on AHR, but on days 26 and 28, AHR was decreased and this continued up to day 30 for all treated groups. Treatment with BTX had no significant effect on the gene expressions of TrkA, TrkB, M1-M5, α7nAChR, TNF-α, and ERK2 proteins, perivascular inflammation, peribronchial inflammation, hyperplasia of the goblet cell and production of mucus. Besides, mice administered with 10 mg/mL BTX perished. The BTX therapy controlled asthma attacks by decreasing AHR and relaxation of ASMs. CONCLUSION: However, BTX had no significant effect on airway inflammation and production of mucus. While using BTX, it is necessary to prescribe safe doses in order to prevent adverse reactions.


Subject(s)
Asthma , Botulinum Toxins , Bronchial Hyperreactivity , Animals , Asthma/metabolism , Botulinum Toxins/metabolism , Botulinum Toxins/therapeutic use , Bronchi/pathology , Disease Models, Animal , Humans , Hyperplasia/pathology , Inflammation/pathology , Mice , Mice, Inbred BALB C , Myocytes, Smooth Muscle , Ovalbumin , Signal Transduction , Tumor Necrosis Factor-alpha/metabolism , alpha7 Nicotinic Acetylcholine Receptor/metabolism , alpha7 Nicotinic Acetylcholine Receptor/therapeutic use
7.
Allergol Immunopathol (Madr) ; 48(6): 646-653, 2020.
Article in English | MEDLINE | ID: mdl-32284261

ABSTRACT

INTRODUCTION AND OBJECTIVES: Allergic asthma is a complex chronic disease of the respiratory system presenting with cough, dyspnea, wheezing and airway obstruction. More than 300 million people of all age spectrums suffer from asthma worldwide. Immunological and inflammatory processes are main contributors to asthma. Cytokines produced by T helper 2 lymphocytes play main roles in asthma development and progression. Silymarin, a therapeutic agent with anti-oxidative properties, is a main component of Silybium marinum. We herein aimed to compare the anti-inflammatory and anti-allergic effects of two silymarin isomers, isosilybin A and silydianin, in the treatment of allergic asthma. MATERIALS AND METHODS: After isolating and purifying isosilybin A and silydianin, Balb/c mouse model of allergic asthma was produced using ovalbumin injection. Seventy mice were categorized into five (1 normal and 4 asthmatic) groups (n = 14 per group). Mice in three of four asthmatic groups were treated with either isosilybin A, silydianin or budesonide. The 4th asthmatic group was used as positive control, with the non-asthmatic group serving as negative control. Airway hyperresponsiveness (AHR) and levels of IL-4, IL-5 and IL-13 in the BAL fluid were determined. Gene expressions of IL-4, IL-5, IL-13 and MUC5ac, as well as IgE serum level were also measured. Cellular composition of BAL fluid and lungs histopathology were finally investigated. RESULTS: Isosilybin A and silydianin reduced eosinophilic infiltration of lungs, IL-4 and IL-5 levels in BAL fluid, IL-4 and IL-5 gene expressions, as well as AHR in Balb/c mouse model of asthma. However, no significant changes were observed in IL-13 level and mucus hyper-secretion. CONCLUSION: According to our study, isosilybin A and silydianin can control main symptoms of asthma by modulating immune responses.


Subject(s)
Anti-Inflammatory Agents/administration & dosage , Asthma/drug therapy , Immunologic Factors/administration & dosage , Silymarin/analogs & derivatives , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/isolation & purification , Asthma/diagnosis , Asthma/immunology , Bronchoalveolar Lavage Fluid/cytology , Bronchoalveolar Lavage Fluid/immunology , Disease Models, Animal , Female , Humans , Immunologic Factors/chemistry , Immunologic Factors/isolation & purification , Isomerism , Mice , Mice, Inbred BALB C , Silymarin/administration & dosage , Silymarin/chemistry , Silymarin/isolation & purification
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