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Nature Sep 2019Fibrosis is observed in nearly every form of myocardial disease. Upon injury, cardiac fibroblasts in the heart begin to remodel the myocardium by depositing excess...
Fibrosis is observed in nearly every form of myocardial disease. Upon injury, cardiac fibroblasts in the heart begin to remodel the myocardium by depositing excess extracellular matrix, resulting in increased stiffness and reduced compliance of the tissue. Excessive cardiac fibrosis is an important factor in the progression of various forms of cardiac disease and heart failure. However, clinical interventions and therapies that target fibrosis remain limited. Here we demonstrate the efficacy of redirected T cell immunotherapy to specifically target pathological cardiac fibrosis in mice. We find that cardiac fibroblasts that express a xenogeneic antigen can be effectively targeted and ablated by adoptive transfer of antigen-specific CD8 T cells. Through expression analysis of the gene signatures of cardiac fibroblasts obtained from healthy and diseased human hearts, we identify an endogenous target of cardiac fibroblasts-fibroblast activation protein. Adoptive transfer of T cells that express a chimeric antigen receptor against fibroblast activation protein results in a significant reduction in cardiac fibrosis and restoration of function after injury in mice. These results provide proof-of-principle for the development of immunotherapeutic drugs for the treatment of cardiac disease.
Topics: Animals; Antigens, Surface; CD8-Positive T-Lymphocytes; Endomyocardial Fibrosis; Fibroblasts; Humans; Immunotherapy, Adoptive; Male; Mice; Ovalbumin; Wound Healing
PubMed: 31511695
DOI: 10.1038/s41586-019-1546-z -
Frontiers in Immunology 2021Asthma is a chronic and recurring airway disease, which related to mast cell activation. Many compounds derived from Chinese herbal medicine has promising effects on...
INTRODUCTION
Asthma is a chronic and recurring airway disease, which related to mast cell activation. Many compounds derived from Chinese herbal medicine has promising effects on stabilizing mast cells and decreasing inflammatory mediator production. Safranal, one of the active compounds from , shows many anti-inflammatory properties. In this study, we evaluated the effect of safranal in ovalbumin (OVA)-induced asthma model. Furthermore, we investigate the effectiveness of safranal on stabilizing mast cell and inhibiting the production of inflammatory mediators in passive systemic anaphylaxis (PSA) model.
METHODS
OVA-induced asthma and PSA model were used to evaluate the effect of safranal Lung tissues were collected for H&E, TB, IHC, and PAS staining. ELISA were used to determine level of IgE and chemokines (IL-4, IL-5, TNF-α, and IFN-γ). RNA sequencing was used to uncovers genes that safranal regulate. Bone marrow-derived mast cells (BMMCs) were used to investigate the inhibitory effect and mechanism of safranal. Cytokine production (IL-6, TNF-α, and LTC) and NF-κB and MAPKs signaling pathway were assessed.
RESULTS
Safranal reduced the level of serum IgE, the number of mast cells in lung tissue were decreased and Th1/Th2 cytokine levels were normalized in OVA-induced asthma model. Furthermore, safranal inhibited BMMCs degranulation and inhibited the production of LTC, IL-6, and TNF-α. Safranal inhibits NF-κB and MAPKs pathway protein phosphorylation and decreases NF-κB p65, AP-1 nuclear translocation. In the PSA model, safranal reduced the levels of histamine and LTC in serum.
CONCLUSIONS
Safranal alleviates OVA-induced asthma, inhibits mast cell activation and PSA reaction. The possible mechanism occurs through the inhibition of the MAPKs and NF-κB pathways.
Topics: Allergens; Animals; Anti-Inflammatory Agents; Asthma; Cell Degranulation; Cyclohexenes; Cytokines; Disease Models, Animal; Disease Susceptibility; Female; Immunoglobulin E; Inflammation Mediators; Mast Cells; Mice; NF-kappa B; Ovalbumin; Signal Transduction; Terpenes
PubMed: 34093515
DOI: 10.3389/fimmu.2021.585595 -
Cells May 2020Asthma is an important issue not only in health but also in economics worldwide. Therefore, asthma animal models have been frequently used to understand the pathogenesis... (Review)
Review
Asthma is an important issue not only in health but also in economics worldwide. Therefore, asthma animal models have been frequently used to understand the pathogenesis of asthma. Recently, in addition to acquired immunity, innate immunity has also been thought to be involved in asthma. Among innate immune cells, group 2 innate lymphoid cells (ILC2s) have been considered to be crucial for eosinophilic airway inflammation by releasing T helper 2 cytokines. Moreover, house dust mites (HDMs) belonging to group 1 act on airway epithelial cells not only as allergens but also as cysteine proteases. The production of interleukin-25 (IL-25), IL-33, and thymic stromal lymphopoietin (TSLP) from airway epithelial cells was induced by the protease activity of HDMs. These cytokines activate ILC2s, and activated ILC2s produce IL-5, IL-9, IL-13, and amphiregulin. Hence, the HDM-induced asthma mouse model greatly contributes to understanding asthma pathogenesis. In this review, we highlight the relationship between ILC2s and the HDM in the asthma mouse model to help researchers and clinicians not only choose a proper asthma mouse model but also to understand the molecular mechanisms underlying HDM-induced asthma.
Topics: Animals; Aspergillus fumigatus; Asthma; Disease Models, Animal; Humans; Immunity, Innate; Lymphocytes; Mice; Ovalbumin; Pyroglyphidae
PubMed: 32397396
DOI: 10.3390/cells9051178 -
Biomedicine & Pharmacotherapy =... Sep 2021Allergic rhinitis (AR) is a common chronic respiratory disease. Asarum heterotropoides (AH) is predicted to be a treatment for allergic diseases, but its therapeutic...
Allergic rhinitis (AR) is a common chronic respiratory disease. Asarum heterotropoides (AH) is predicted to be a treatment for allergic diseases, but its therapeutic effect is unclear. We aimed to determine the anti-allergic effects of AH in mice with ovalbumin (OVA)-induced AR. OVA-induced AR mouse model was constructed, and AH was orally administered for a week; next, nasal clinical symptoms were evaluated. The levels of serum histamine, OVA-specific IgE, and IL-13 were measured by ELISA. Inflammatory cells, including leukocytes, neutrophils, eosinophils, and macrophages were counted in the nasal lavage fluid (NALF). Histopathological examinations of the nasal tissues were performed using H&E, Giemsa, and PAS staining. The production of periostin and eotaxin-3 from AH-treated human nasal epithelial cells (HNEpCs) in vitro, was measured using ELISA. Oral administration of AH alleviated allergic symptoms in mice with AR; significantly decreased levels of allergic mediators, such as serum histamine and OVA-specific IgE. The decrease in allergic symptoms positively correlated with the decrease in serum allergic mediators. The NALF of AH-treated AR mice demonstrated lower number of eosinophils. AH demonstrated a capacity to reduce the infiltration of mast cells, eosinophils, and goblet cells, thereby resulting in thinner nasal tissues. Moreover, treatment of HNEpCs with AH demonstrated suppressed production of periostin and eotaxin-3. AH exerts a therapeutic effect in modulating AR through multi-target and multi-function influence on regulating B cells, mast cells, eosinophils, goblet cells, and epithelial cells.
Topics: Animals; Anti-Allergic Agents; Asarum; Disease Models, Animal; Female; Humans; Mice; Mice, Inbred BALB C; Ovalbumin; Plant Extracts; Rhinitis, Allergic
PubMed: 34328098
DOI: 10.1016/j.biopha.2021.111944 -
Frontiers in Immunology 2022Asthma is a chronic respiratory disease highly prevalent worldwide. Recent studies have suggested a role for microbiome-associated gut-lung axis in asthma development....
The Ability of Resveratrol to Attenuate Ovalbumin-Mediated Allergic Asthma Is Associated With Changes in Microbiota Involving the Gut-Lung Axis, Enhanced Barrier Function and Decreased Inflammation in the Lungs.
Asthma is a chronic respiratory disease highly prevalent worldwide. Recent studies have suggested a role for microbiome-associated gut-lung axis in asthma development. In the current study, we investigated if Resveratrol (RES), a plant-based polyphenol, can attenuate ovalbumin (OVA)-induced murine allergic asthma, and if so, the role of microbiome in the gut-lung axis in this process. We found that RES attenuated allergic asthma with significant improvements in pulmonary functions in OVA-exposed mice when tested using plethysmography for frequency (F), mean volume (MV), specific airway resistance (sRaw), and delay time(dT). RES treatment also suppressed inflammatory cytokines in the lungs. RES modulated lung microbiota and caused an abundance of A accompanied by a reduction of LPS biosynthesis in OVA-treated mice. Furthermore, RES also altered gut microbiota and induced enrichment of significantly in the colon accompanied by an increase in butyric acid concentration in the colonic contents from OVA-treated mice. Additionally, RES caused significant increases in tight junction proteins and decreased mucin (Muc5ac) in the pulmonary epithelium of OVA-treated mice. Our results demonstrated that RES may attenuate asthma by inducing beneficial microbiota in the gut-lung axis and through the promotion of normal barrier functions of the lung.
Topics: Animals; Asthma; Disease Models, Animal; Inflammation; Lung; Mice; Microbiota; Ovalbumin; Resveratrol
PubMed: 35265071
DOI: 10.3389/fimmu.2022.805770 -
The Journal of Allergy and Clinical... Jun 2021Lung nociceptor neurons amplify immune cell activity and mucus metaplasia in response to an inhaled allergen challenge in sensitized mice.
BACKGROUND
Lung nociceptor neurons amplify immune cell activity and mucus metaplasia in response to an inhaled allergen challenge in sensitized mice.
OBJECTIVE
We sought to identify the cellular mechanisms by which these sensory neurons are activated subsequent to allergen exposure.
METHODS
We used calcium microscopy and electrophysiologic recording to assess whether vagal neurons directly respond to the model allergen ovalbumin (OVA). Next, we generated the first nociceptor-specific FcεR1γ knockdown (TRPV1::FcεR1γ) mice to assess whether this targeted invalidation would affect the severity of allergic inflammation in response to allergen challenges.
RESULTS
Lung-innervating jugular nodose complex ganglion neurons express the high-affinity IgE receptor FcεR1, the levels of which increase in OVA-sensitized mice. FcεR1γ-expressing vagal nociceptor neurons respond directly to OVA complexed with IgE with depolarization, action potential firing, calcium influx, and neuropeptide release. Activation of vagal neurons by IgE-allergen immune complexes, through the release of substance P from their peripheral terminals, directly amplifies T2 cell influx and polarization in the airways. Allergic airway inflammation is decreased in TRPV1::FcεR1γ mice and in FcεR1α mice into which bone marrow has been transplanted. Finally, increased in vivo circulating levels of IgE following allergen sensitization enhances the responsiveness of FcεR1 to immune complexes in both mouse jugular nodose complex ganglion neurons and human induced pluripotent stem cell-derived nociceptors.
CONCLUSIONS
Allergen sensitization triggers a feedforward inflammatory loop between IgE-producing plasma cells, FcεR1-expressing vagal sensory neurons, and T2 cells, which helps to both initiate and amplify allergic airway inflammation. These data highlight a novel target for reducing allergy, namely, FcεR1γ expressed by nociceptors.
Topics: Allergens; Animals; Calcium; Disease Models, Animal; Disease Susceptibility; Gene Expression; Genetic Predisposition to Disease; Hypersensitivity; Mice; Mice, Knockout; Neurons; Nociceptors; Ovalbumin; Receptors, IgE; Respiratory Mucosa; Substance P; Vagus Nerve
PubMed: 33453289
DOI: 10.1016/j.jaci.2020.12.644 -
Advanced Healthcare Materials Mar 2021Widespread vaccination is essential to global health. Significant barriers exist to improving vaccine coverage in lower- and middle-income countries, including the...
Widespread vaccination is essential to global health. Significant barriers exist to improving vaccine coverage in lower- and middle-income countries, including the costly requirements for cold-chain distribution and trained medical personnel to administer the vaccines. A heat-stable and highly porous tablet vaccine that can be administered sublingually via simple dissolution under the tongue is described. SIMPL tablet vaccines (Supramolecular IMmunization with Peptides subLingually) are produced by freeze-drying a mixture of self-assembling peptide-polymer nanofibers, sugars, and adjuvant. Sublingual immunization with SIMPL tablets raises antibody responses against both a model epitope from ovalbumin and a clinically relevant epitope from Mycobacterium tuberculosis. Further, sublingual antibody responses are not diminished after heating the tablets for 1 week at 45 °C, in contrast to a more conventional carrier vaccine (KLH). This approach directly addresses the need for a heat-stable and easily deliverable vaccine to improve equity in global vaccine coverage.
Topics: Administration, Sublingual; Epitopes; Immunization; Ovalbumin; Peptides
PubMed: 33634607
DOI: 10.1002/adhm.202001614 -
Talanta Apr 2021SARS-COV-2 is a novel coronavirus discovered in Wuhan in December 30, 2019, and is a family of SARS-COV (severe acute respiratory syndrome coronavirus), that is,... (Review)
Review
SARS-COV-2 is a novel coronavirus discovered in Wuhan in December 30, 2019, and is a family of SARS-COV (severe acute respiratory syndrome coronavirus), that is, coronavirus family. After infection with SARS-COV-2, patients often experience fever, cough, gas prostration, dyspnea and other symptoms, which can lead to severe acute respiratory syndrome (SARS), kidney failure and even death. The SARS-COV-2 virus is particularly infectious and has led to a global infection crisis, with an explosion in the number of infections. Therefore, rapid and accurate detection of the virus plays a vital role. At present, many detection methods are limited in their wide application due to their defects such as high preparation cost, poor stability and complex operation process. Moreover, some methods need to be operated by professional medical staff, which can easily lead to infection. In order to overcome these problems, a Surface molecular imprinting technology (SM-MIT) is proposed for the first time to detect SARS-COV-2 virus. For this SM-MIT method, this review provides detailed detection principles and steps. In addition, this method not only has the advantages of low cost, high stability and good specificity, but also can detect whether it is infected at designated points. Therefore, we think SM-MIT may have great potential in the detection of SARS-COV-2 virus.
Topics: COVID-19; Humans; Magnetite Nanoparticles; Microspheres; Molecular Imprinting; Ovalbumin; Polymers; SARS-CoV-2; Sensitivity and Specificity; Viral Proteins
PubMed: 33592725
DOI: 10.1016/j.talanta.2020.121977 -
International Journal of Biological... Aug 2019The surface properties and foaming of ovalbumin and guar gum aqueous solutions was investigated in the presence of sucrose or sorbitol. All solutions had a broad...
The surface properties and foaming of ovalbumin and guar gum aqueous solutions was investigated in the presence of sucrose or sorbitol. All solutions had a broad particle size distribution (395.60 at 1137.50 nm). Higher ovalbumin concentrations had lower equilibrium surface tension and higher absolute values of the zeta potential, regardless the presence of sucrose or sorbitol. Mixtures containing ovalbumin and guar gum resulted in a predominantly elastic character of the air-water interface probably due to the formation of a complex (hydrogen bonding and/or hydrophobic interactions) between ovalbumin and guar gum. Besides, the increase in guar gum concentration enhanced the elasticity of the surface film. Higher concentrations of both polymers were required to provide higher kinetic stability to the system, although the increase in guar gum concentration reduced foam capacity due to the increase in the apparent viscosity. Foams formed in the presence of sucrose or sorbitol showed similar half-lives.
Topics: Galactans; Mannans; Ovalbumin; Particle Size; Plant Gums; Rheology; Sorbitol; Sucrose; Surface Properties; Surface Tension; Viscoelastic Substances
PubMed: 31128179
DOI: 10.1016/j.ijbiomac.2019.05.140 -
Methods in Molecular Biology (Clifton,... 2022Aeroallergens are common inducers of asthma in humans and are widely used in experimental research to generate animal models of this disease. In this chapter, we...
Aeroallergens are common inducers of asthma in humans and are widely used in experimental research to generate animal models of this disease. In this chapter, we describe four mouse models of aeroallergen-induced asthma. These models differ in type and number of allergens used, route and duration of allergen exposure, and utilization of an adjuvant, representing different mechanistic variants of asthma. In addition, we describe several basic methods that are commonly used in mechanistic studies of asthma in mice. These methods include tracheotomy and bronchoalveolar lavage, cytospin and morphologic analysis of bronchoalveolar lavage cells, and lung harvest and digestion for generation of single-cell suspension.
Topics: Allergens; Animals; Asthma; Bronchoalveolar Lavage Fluid; Disease Models, Animal; Lung; Mice; Mice, Inbred BALB C; Ovalbumin
PubMed: 35771460
DOI: 10.1007/978-1-0716-2364-0_1