RGFP966, a selective HDAC3 inhibitor, ameliorates allergic and inflammatory responses in an OVA-induced allergic rhinitis mouse model

2021 ◽  
Vol 93 ◽  
pp. 107400
Author(s):  
Weitian Zhang ◽  
Xiwen Sun ◽  
Guangyi Ba ◽  
Ru Tang ◽  
Hai Lin
Keyword(s):  
Allergic Rhinitis ◽  
Mouse Model ◽  
Inflammatory Responses

scholarly journals A Herbal Concoction of Cinnamomum cassia and Artemisa annua Extracts Ameliorates Allergic Rhinitis in OVA-Induced Balb/C Mice by Inhibiting Th2 Signaling

2021 ◽  
Vol 12 (1) ◽  
pp. 340
Author(s):  
Chuhyun Bae ◽  
Jisoo Kim ◽  
Soodong Park ◽  
Jaejung Shim ◽  
Junglyoul Lee
Keyword(s):  
Allergic Rhinitis ◽  
Mouse Model ◽  
Inflammatory Responses ◽  
Airway Disease ◽  
Treated Group ◽  
Respiratory Epithelium ◽  
Therapeutic Effects ◽  
Cinnamomum Cassia ◽  
Inflammatory Airway Disease ◽  
Artemisa Annua

Allergic rhinitis (AR) is an inflammatory airway disease (IAD) that is characterized by itching, nasal obstruction, and sneezing. AR is induced by Th-2 inflammatory responses such as those mediated by IgE and IL-4. This study aims to investigate the therapeutic effects of an herbal concoction, which is a combination of Cinnamomum cassia and Artemisa annua extracts (CIAR) against ovalbumin (OVA)-induced allergic rhinitis in a Balb/C mouse model. The effect of CIAR on the Th-2 mediated inflammatory response in the AR mouse model was studied by analyzing blood or nasal fluid samples. Experimental results revealed that OVA inhalation increased IgE, IL-4, IL-33, and TSLP levels, leading to Th2-type cytokine response. CIAR was found to significantly reduce the Th-2 response and levels of cytokines, including IL-4, IL-33, and thymic stromal lymphopoietin (TSLP). CIAR also down-regulated eosinophil (EOS) and basophil (BASO) levels in the blood. Histological analyses demonstrated decreased OVA-induced thickness of the respiratory epithelium in the CIAR-treated group. Collectively, our results suggest that the herbal concoction CIAR can effectively ameliorate the development of allergic rhinitis through the inhibition of Th-2 mediated responses.

scholarly journals Atorvastatin Inhibits Endothelial PAI-1-Mediated Monocyte Migration and Alleviates Radiation-Induced Enteropathy

2021 ◽  
Vol 22 (4) ◽  
pp. 1828
Author(s):  
Seo Young Kwak ◽  
Sunhoo Park ◽  
Hyewon Kim ◽  
Sun-Joo Lee ◽  
Won-Suk Jang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Inflammatory Responses ◽  
Umbilical Vein ◽  
Plasminogen Activator Inhibitor ◽  
Endothelial Damage ◽  
Plasminogen Activator Inhibitor 1 ◽  
Monocyte Migration ◽  
Radiation Induced ◽  
Umbilical Vein Endothelial Cells ◽  
Pai 1

Intestinal injury is observed in cancer patients after radiotherapy and in individuals exposed to radiation after a nuclear accident. Radiation disrupts normal vascular homeostasis in the gastrointestinal system by inducing endothelial damage and senescence. Despite advances in medical technology, the toxicity of radiation to healthy tissue remains an issue. To address this issue, we investigated the effect of atorvastatin, a commonly prescribed hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor of cholesterol synthesis, on radiation-induced enteropathy and inflammatory responses. We selected atorvastatin based on its pleiotropic anti-fibrotic and anti-inflammatory effects. We found that atorvastatin mitigated radiation-induced endothelial damage by regulating plasminogen activator inhibitor-1 (PAI-1) using human umbilical vein endothelial cells (HUVECs) and mouse model. PAI-1 secreted by HUVECs contributed to endothelial dysfunction and trans-endothelial monocyte migration after radiation exposure. We observed that PAI-1 production and secretion was inhibited by atorvastatin in irradiated HUVECs and radiation-induced enteropathy mouse model. More specifically, atorvastatin inhibited PAI-1 production following radiation through the JNK/c-Jun signaling pathway. Together, our findings suggest that atorvastatin alleviates radiation-induced enteropathy and supports the investigation of atorvastatin as a radio-mitigator in patients receiving radiotherapy.

scholarly journals The effect of Co-Q10 on allergic rhinitis and allergic asthma

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Qixue Du ◽  
Wei Meng ◽  
Seyyed Shamsadin Athari ◽  
Renzhong Wang
Keyword(s):  
Allergic Rhinitis ◽  
Animal Models ◽  
Allergic Asthma ◽  
Inflammatory Responses ◽  
Lavage Fluid ◽  
Inflammatory Factors ◽  
Stress Injury ◽  
Antioxidant Genes ◽  
Histamine Production ◽  
Nrf2 Expression

Abstract Background Allergic asthma is an inflammatory disease resulting from continued or intermittent allergen exposure, and allergic rhinitis can be trigger of asthma. The main mechanism of these disease is allergic reaction and immune response dysregulation. Co-Q10 is an enzyme cofactor in mitochondria can control asthma and allergic rhinitis symptoms. In the present study, we determined that the CoQ10-induced anti-allergic effects were mediated by up-regulation of Nrf2. Methods Animal models of allergic rhinitis and allergic asthma were produced and treated with Co-Q10, Co-Q10 and O-3, Co-Q10 and Mg-S. Bronchoalveolar lavage fluid was collected from animal models, and IL-4, 5, 13, INF-y, Eicosanoids, IgE, EPO, and histamine production were measured. Also, COX-2, CCL24, CCL11, Nrf2, Eotaxin, Cytb, COX1 and ND1 genes expressions and histopathology were studied. BALf's cells were collected by tracheostomy and used in slide producing by cytospine. Cytokines, Eicosanoids, IgE, EPO, and histamine were measured by ELISA method. Gene expression was done by Real-time PCR. Results Co-Q10 with two supplementation (Mg-S and O-3) modulate MRC, BALf eosinophils, eosinophilic inflammation related genes (eotaxin, CCL11 and CCL24), peribronchial and perivascular inflammation, EPO, type 2 cytokines (IL-4, 5 and 13), IgE, histamine, Cyc-LT and LTB4 as main allergic bio-factors. Importantly, Co-Q10 treatment increased Nrf2 expression and Nrf2 induced antioxidant genes, glutathione redox and inhibited inflammation, oxidative stress injury, Th2 cytokines production and attenuated allergic inflammatory responses. Conclusion Nrf2 is activated in response to allergen, induces resistance against the rhinitis and asthma development and plays an essential role in broncho-protection. Co-Q10 increases the Nrf2 expression and the Nrf2 over-expression has strong effect in control of type2 cytokines, allergic mediators and inflammatory factors that lead to harnessing of allergy and asthma. Graphic abstract

scholarly journals Metabolic Profiling of Suprachiasmatic Nucleus Reveals Multifaceted Effects in an Alzheimer’s Disease Mouse Model

2021 ◽  
pp. 1-12
Author(s):  
Muhamed N.H. Eeza ◽  
Rico Singer ◽  
Corinna Höfling ◽  
Jörg Matysik ◽  
Huub J.M. de Groot ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Metabolic Profiling ◽  
Inflammatory Responses ◽  
Immunohistochemical Analysis ◽  
Magic Angle Spinning ◽  
Tg2576 Mouse ◽  
Magic Angle ◽  
Gaba Production

Background: Circadian rhythm disturbance is commonly observed in Alzheimer’s disease (AD). In mammals, these rhythms are orchestrated by the superchiasmatic nucleus (SCN). Our previous study in the Tg2576 AD mouse model suggests that inflammatory responses, most likely manifested by low GABA production, may be one of the underlying perpetrators for the changes in circadian rhythmicity and sleep disturbance in AD. However, the mechanistic connections between SCN dysfunction, GABA modulation, and inflammation in AD is not fully understood. Objective: To reveal influences of amyloid pathology in Tg2576 mouse brain on metabolism in SCN and to identify key metabolic sensors that couple SCN dysfunction with GABA modulation and inflammation. Methods: High resolution magic angle spinning (HR-MAS) NMR in conjunction with multivariate analysis was applied for metabolic profiling in SCN of control and Tg2576 female mice. Immunohistochemical analysis was used to detect neurons, astrocytes, expression of GABA transporter 1 (GAT1) and Bmal1. Results: Metabolic profiling revealed significant metabolic deficits in SCN of Tg2576 mice. Reductions in glucose, glutamate, GABA, and glutamine provide hints toward an impaired GABAergic glucose oxidation and neurotransmitter cycling in SCN of AD mice. In addition, decreased redox co-factor NADPH and glutathione support a redox disbalance. Immunohistochemical examinations showed low expression of the core clock gene, Bmal1, especially in activated astrocytes. Moreover, decreased expression of GAT1 in astrocytes indicates low GABA recycling in this cell type. Conclusion: Our results suggest that redox disbalance and compromised GABA signaling are important denominators and connectors between neuroinflammation and clock dysfunction in AD.

scholarly journals Study of the effect exerted by fructo-oligosaccharides from yacon (Smallanthus sonchifolius) root flour in an intestinal infection model with Salmonella Typhimurium

2012 ◽  
Vol 109 (11) ◽  
pp. 1971-1979 ◽  
Author(s):  
Eva Velez ◽  
Natalia Castillo ◽  
Oscar Mesón ◽  
Alfredo Grau ◽  
María E. Bibas Bonet ◽  
...  
Keyword(s):  
Mouse Model ◽  
Protective Effect ◽  
Salmonella Enteritidis ◽  
Inflammatory Responses ◽  
Intestinal Barrier ◽  
Secretory Iga ◽  
Infection Model ◽  
Enteric Infection ◽  
Smallanthus Sonchifolius ◽  
Iga Production

Beneficial effects of prebiotics like inulin and fructo-oligosaccharides (FOS) have been proven in health and nutrition. Yacon (Smallanthus sonchifolius), an Andean crop, contains FOS (50–70 % of its dry weight) and, therefore, is considered a prebiotic. Commercial FOS can up-regulate total secretory IgA (S-IgA) in infant mice, prevent infection with Salmonella in swine or enhance immune response for Salmonella vaccine in a mouse model. Previously, we found that administration of yacon root flour regulates gut microbiota balance and has immunomodulatory effects without inflammatory responses. The aim of the present paper is to analyse if yacon prevents enteric infection caused by a strain of Salmonella enteritidis serovar Typhimurium (S. Typhimurium) in a mouse model. BALB/c mice were supplemented with yacon flour (45 d), challenged with S. Typhimurium and killed to study pathogen translocation, total and specific IgA production by ELISA, presence of IgA and other cytokines and Toll-like receptor 4 (TLR4) and clustor of differentiation 206 (CD206) receptors positive cells by immunofluorescence and histological changes. Yacon flour administration had a protective effect from 15 to 30 d of treatment. We found a peak of total S-IgA production without translocation of the pathogen for these periods. At 30 d, there was an increase in IL-6 and macrophage inflammatory proteins-1α+ cells and expression of the receptors CD206 and TLR4. Yacon flour did not have incidence in pathogen-specific S-IgA production. Longer periods (45 d) of administration had no protective effect. Therefore, yacon can prevent enteric infection caused by S. Typhimurium when given up to 30 d; this effect would be mediated by enhancing non-specific immunity, such as total S-IgA, that improves the immunological intestinal barrier.

GlcNAc is a mast-cell chromatin-remodeling oncometabolite that promotes systemic mastocytosis aggressiveness

Blood ◽  
2021 ◽  
Author(s):  
Julie Agopian ◽  
Quentin Da Costa ◽  
Quang Vo Nguyen ◽  
Giulia Scorrano ◽  
Paraskevi Kousteridou ◽  
...  
Keyword(s):  
Mouse Model ◽  
Tyrosine Kinases ◽  
Inflammatory Responses ◽  
Immunoglobulin E ◽  
Therapeutic Potential ◽  
Systemic Mastocytosis ◽  
High Plasma ◽  
Humanized Mouse Model ◽  
Acute Response ◽  
Genes Encoding

Systemic mastocytosis (SM) is a KIT-driven hematopoietic neoplasm characterized by the excessive accumulation of neoplastic mast cells (MCs) in various organs and, mainly, the bone marrow (BM). Multiple genetic and epigenetic mechanisms contribute to the onset and severity of SM. However, little is known to date about the metabolic underpinnings underlying SM aggressiveness, which has thus far impeded the development of strategies to leverage metabolic dependencies when existing KIT-targeted treatments fail. Here, we show that plasma metabolomic profiles were able to discriminate indolent from advanced forms of the disease. We identified N-acetyl-D-glucosamine (GlcNAc) as the most predictive metabolite of SM severity. High plasma levels of GlcNAc in patients with advanced SM correlated with the activation of the GlcNAc-fed hexosamine biosynthesis pathway (HBP) in patients BM aspirates and purified BM MCs. At the functional level, GlcNAc enhanced human neoplastic MCs proliferation and promoted rapid health deterioration in a humanized mouse model of SM. In addition, in the presence of GlcNAc, immunoglobulin E-stimulated MCs triggered enhanced release of proinflammatory cytokines and a stronger acute response in a mouse model of passive cutaneous anaphylaxis. Mechanistically, elevated GlcNAc levels promoted the transcriptional accessibility of chromatin regions that contain genes encoding mediators of receptor tyrosine kinases cascades and inflammatory responses, thus leading to a more aggressive phenotype. Therefore, GlcNAc is an oncometabolite driver of SM aggressiveness. This study suggests the therapeutic potential for targeting metabolic pathways in MC-related diseases to manipulate MCs effector functions.

Therapeutic potential of α-lipoic acid derivative, sodium zinc histidine dithiooctanamide, in a mouse model of allergic rhinitis

2017 ◽  
Vol 7 (11) ◽  
pp. 1095-1103
Author(s):  
Toshiaki Nakano ◽  
Li-Wen Hsu ◽  
Chia-Yun Lai ◽  
Yuki Takaoka ◽  
Masafumi Inomata ◽  
...  
Keyword(s):  
Allergic Rhinitis ◽  
Mouse Model ◽  
Acid Derivative ◽  
Lipoic Acid ◽  
Therapeutic Potential ◽  
Sodium Zinc

Role of Superantigens in Allergic Inflammation: Their Relationship to Allergic Rhinitis, Chronic Rhinosinusitis, Asthma, and Atopic Dermatitis

2018 ◽  
Vol 32 (6) ◽  
pp. 502-517 ◽  
Author(s):  
Nuray Bayar Muluk ◽  
Fazilet Altın ◽  
Cemal Cingi
Keyword(s):  
T Cells ◽  
Allergic Rhinitis ◽  
Atopic Dermatitis ◽  
Inflammatory Response ◽  
Chronic Rhinosinusitis ◽  
Inflammatory Responses ◽  
Immunoglobulin E ◽  
Severe Disease ◽  
Allergic Inflammation ◽  
Allergic Dermatitis

Objectives Our intention was to review all material published to date regarding superantigens (SAgs) and allergy from an otorhinolaryngological viewpoint to understand this association more clearly. Methods We identified all materials published mentioning both SAg and allergic rhinitis (AR), chronic sinusitis, asthma, and atopic dermatitis (AD) that are indexed on PubMed, Google, or the ProQuest Central databases. Results Staphylococcus aureus is a significant bacterial pathogen in humans and has the ability to produce enterotoxins with superantigenic features. The inflammatory response in allergy seen in both B cell and T cell may be attributed to SAgs. Sufferers of both allergic asthma with rhinitis and AR alone produce serological evidence of immunoglobulin E formation to SAgs produced by S. aureus. Perennial AR sufferers carry S. aureus more frequently and the presence of the organism within the nasal cavity may exacerbate perennial AR. SAg produced by S. aureus potentially worsens the asthmatic inflammatory response within the airway and may lead to the airways becoming hyperresponsive, as well as possibly activating T cells if asthmatic control is poor. Staphylococcal SAgs potentially increase the risk of developing chronic rhinosinusitis with nasal polyposis, additionally being a marker for more severe disease. If SAgs bring about chronic inflammatory responses in the nose and sinuses, then T cells excreting interferon-gamma may be a crucial mediator. In allergic dermatitis, S. aureus could be a key player in exacerbation of the condition. Even in younger pediatric patients with allergic dermatitis, allergic hypersensitivity to SAgs is frequent and may be a factor explaining how severe the condition becomes. Conclusion Just as SAgs are known to feature in many allergic conditions, they play their part in AR, chronic rhinosinusitis, asthma, and AD. Further research is required before the relationship between SAgs and allergy can be adequately explained.

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