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

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

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MicroRNA-182-5p relieves murine allergic rhinitis via TLR4/NF-κB pathway

Open Medicine ◽

10.1515/med-2020-0198 ◽

2020 ◽

Vol 15 (1) ◽

pp. 1202-1212

Author(s):

Aichun Zhang ◽

Yangzi Jin

Keyword(s):

Allergic Rhinitis ◽

Inflammatory Cells ◽

Lavage Fluid ◽

Specific Ige ◽

Inflammatory Factors ◽

Pcr Analysis ◽

Reverse Transcription Pcr ◽

Pathway Activation ◽

Nasal Lavage Fluid

AbstractAllergic rhinitis (AR) is one of the most common chronic diseases. This study examined whether microRNA (miR)-182-5p plays a role in AR by regulating toll-like receptor 4 (TLR4). First, data demonstrated that TLR4 was a target of miR-182-5p. Subsequently, AR mouse model was established to explore the role of miR-182-5p and TLR4 in AR in vivo. Initially, quantitative reverse transcription-PCR (qRT-PCR) analysis indicated that miR-182-5p was downregulated, while TLR4 expression was upregulated in AR mice. Then we found that miR-182-5p mimic reduced the frequency of sneezing and nose rubbing of the AR mice. In addition, miR-182-5p mimic significantly increased ovalbumin (OVA)-specific IgE and leukotriene C4 expression levels in nasal lavage fluid (NLF) and serum of AR mice. miR-182-5p mimic decreased the number of inflammatory cells in NLF of AR mice. It also reduced the levels of inflammatory factors in the serum of AR mice, such as interleukin (IL)-4, IL-5, IL-13, IL-17 and tumor necrosis factor (TNF)-α, while increasing the release of IFN-γ and IL-2. Finally, miR-182-5p mimic inhibited NF-κB signaling pathway activation in AR mice. However, all effects of miR-182-5p mimic on AR mice were reversed by TLR4-plasmid. In conclusion, miR-182-5p/TLR4 axis may represent a novel therapeutic target for AR.

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CD8+ Tregs Ameliorate Inflammatory Reactions in a Murine Model of Allergic Rhinitis

10.21203/rs.3.rs-212586/v1 ◽

2021 ◽

Author(s):

Lin Lin ◽

Fei Dai ◽

Jinjin Wei ◽

Zheng Chen

Keyword(s):

Allergic Rhinitis ◽

Cell Cultures ◽

Murine Model ◽

Transforming Growth Factor ◽

Inflammatory Responses ◽

Lavage Fluid ◽

Inflammatory Reactions ◽

Inflammatory Conditions ◽

Nasal Lavage Fluid

Abstract Background CD8+CD25+fork-head box transcription factor (Foxp3)+ regulatory T cells (CD8+ Tregs) play a role in immune tolerance. However, the role of these cells in allergic rhinitis (AR) has not been elucidated. The study aimed to evaluate influences of CD8+ Tregs on inflammatory conditions in a murine model of AR. Methods A murine model of AR was established. CD8+ Tregs were isolated from mice nasal mucosa and cultured in vitro. We examined interleukin (IL)-10 and transforming growth factor (TGF)-β in cell cultures. Then, we administered CD8+ Tregs into mice nasal mucosal cultures, and examined eosinophil cation protein (ECP), IL-4, IL-5 and IL-13 in these cultures. Finally, we adoptively transferred CD8+ Tregs into mice models, and evaluated percentages of CD8+ Tregs, numbers of sneezing and nasal rubbing, and counts of eosinophils and contents of ECP, IL-4, IL-5, IL-13, IL-10 and TGF-β in nasal lavage fluid (NLF) in mice. Results The percentage of CD8+ Tregs from AR mice was reduced. IL-10 and TGF-β were increased in cell cultures from AR mice. ECP, IL-4, IL-5 and IL-13 were decreased after the AR mice CD8+ Tregs administration in mucosal cultures. However, their contents were not changed after normal CD8+ Tregs treatment. Additionally, the adoptive transfer of AR CD8+ Tregs enhanced the percentage of CD8+ Tregs and levels of IL-10 and TGF-β in NLF, reduced numbers of sneezing and nasal rubbing, and counts of eosinophils and concentrations of ECP, IL-4, IL-5 and IL-13 in NLF. However, normal CD8+ Tregs could not change above parameters. Conclusion These findings show that CD8+ Tregs may inhibit inflammatory responses in the AR condition.

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Prophylactic treatment with MSC-derived exosomes attenuates traumatic acute lung injury in rats

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00391.2018 ◽

2019 ◽

Vol 316 (6) ◽

pp. L1107-L1117 ◽

Cited By ~ 17

Author(s):

Qing-Chun Li ◽

Yun Liang ◽

Zhen-Bo Su

Keyword(s):

Oxidative Stress ◽

Acute Lung Injury ◽

Lung Injury ◽

Purinergic Receptor ◽

Dry Weight ◽

Lavage Fluid ◽

Inflammatory Factors ◽

Sprague Dawley ◽

Stress Injury ◽

Potential Strategy

The mesenchymal stem cell (MSC) is a potential strategy in the pretreatment of traumatic acute lung injury (ALI), a disease that causes inflammation and oxidative stress. This study aimed to investigate whether MSC-exosomal microRNA-124-3p (miR-124-3p) affects traumatic ALI. Initially, a traumatic ALI rat model was established using the weight-drop method. Then, exosomes were obtained from MSCs of Sprague-Dawley rats, which were injected into the traumatic ALI rats. We found that miR-124-3p was abundantly-expressed in MSCs-derived exosomes and could directly target purinergic receptor P2X ligand-gated ion channel 7 (P2X7), which was overexpressed in traumatic ALI rats. After that, a loss- and gain-of-function study was performed in MSCs and traumatic ALI rats to investigate the role of miR-124-3p and P2X7 in traumatic ALI. MSC-derived exosomal miR-124-3p or silenced P2X7 was observed to increase the survival rate of traumatic ALI rats and enhance the glutathione/superoxide dismutase activity in their lung tissues. However, the wet/dry weight of lung tissues, activity of methylenedioxyamphetamine and H2O2, and levels of inflammatory factors (TNF-a, IL-6, and IL-8) were reduced. Similarly, the numbers of total cells, macrophages, neutrophils, and lymphocytes in bronchoalveolar lavage fluid were also reduced when treated with exosomal miR-124-3p or silenced P2X7. In conclusion, the results provide evidence that miR-124-3p transferred by MSC-derived exosomes inhibited P2X7 expression, thus improving oxidative stress injury and suppressing inflammatory response in traumatic ALI, highlighting a potential pretreatment for traumatic ALI.

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Effect of the potent and selective DP1 receptor antagonist, asapiprant (S-555739), in animal models of allergic rhinitis and allergic asthma

European Journal of Pharmacology ◽

10.1016/j.ejphar.2015.08.003 ◽

2015 ◽

Vol 765 ◽

pp. 15-23 ◽

Cited By ~ 12

Author(s):

Go Takahashi ◽

Fujio Asanuma ◽

Noriko Suzuki ◽

Maki Hattori ◽

Shingo Sakamoto ◽

...

Keyword(s):

Allergic Rhinitis ◽

Animal Models ◽

Receptor Antagonist ◽

Allergic Asthma

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Studying the Effects of Vitamin A on the Severity of Allergic Rhinitis and Asthma

Iranian Journal of Allergy Asthma and Immunology ◽

10.18502/ijaai.v20i6.8018 ◽

2021 ◽

Author(s):

Linlin Feng ◽

Fengyan Sun ◽

Yan Chen ◽

Seyyed Shamsadin Athari ◽

Xiaoyun Chen

Keyword(s):

Allergic Rhinitis ◽

Immune System ◽

Vitamin A ◽

Allergic Asthma ◽

Peroxidase Activity ◽

Inflammatory Responses ◽

Vitamin A Deficiency ◽

Allergic Diseases ◽

Leukotriene B4 ◽

Eosinophil Peroxidase

Allergic asthma is a complex lung disease characterized by breathlessness, airway inflammation, and obstruction. Allergy and allergic rhinitis (AR) are the main triggers of asthma. Vitamin A is an important supplementary factor for the physiological activation of the immune system. In the present study, we investigated the effects of vitamin A on the exacerbation of allergic asthma symptoms. BALB/c mice were allocated to four groups. Asthma was created in two groups, and in the other two groups, rhinitis was induced. One of the asthma groups and one of the rhinitis groups orally received vitamin A (20 IU/g for 15 days). The levels of Immunoglobulin (Ig) E, histamine, leukotriene B4 (LTB4), Cysteinyl leukotriene receptor (Cys-LT), interleukin (IL)-4, IL-5, IL-13, and IL-35 as well as eosinophil peroxidase activity, were measured. Also, the histopathology of mice lungs was evaluated. The levels of total IgE, LTB4, Cys-LT, IL-4, IL-5, IL-17, and IL-33, eosinophil peroxidase activity, perivascular and peribronchial inflammation significantly decreased in vitamin A-treated asthma and rhinitis groups compared to non-treated groups. Also, IL-13 and histamine levels, hyperplasia of the goblet cell, and hyper-secretion of the mucus insignificantly decreased in vitamin A-treated asthma and rhinitis groups. Asthma and AR are common diseases that are generally developed due to the dysregulation of the immune system. Vitamin A plays an important role in controlling the immunopathologic mechanisms of allergic diseases. Vitamin A could be a useful supplement in managing AR and asthma by decreasing the severity of inflammatory responses. Therefore, control of vitamin A deficiency is recommended in Allergy.

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CD8+ Tregs ameliorate inflammatory reactions in a murine model of allergic rhinitis

Allergy Asthma & Clinical Immunology ◽

10.1186/s13223-021-00577-8 ◽

2021 ◽

Vol 17 (1) ◽

Author(s):

Lin Lin ◽

Fei Dai ◽

Jinjin Wei ◽

Zheng Chen

Keyword(s):

Allergic Rhinitis ◽

Cell Cultures ◽

Murine Model ◽

Transforming Growth Factor ◽

Inflammatory Responses ◽

Lavage Fluid ◽

Inflammatory Reactions ◽

Inflammatory Conditions ◽

Nasal Lavage Fluid

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Sequential degranulation of eosinophils induced by antigen or autocoids in allergic humans

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100143390 ◽

1986 ◽

Vol 44 ◽

pp. 354-355

Author(s):

Kate W. Sjoerdsma ◽

W. James Metzger

Keyword(s):

Allergic Rhinitis ◽

Bronchoalveolar Lavage ◽

Allergic Asthma ◽

Skin Test ◽

Positive Skin Test ◽

Positive Skin ◽

Human Eosinophil ◽

Asthmatic Patients ◽

Allergic Asthmatic ◽

History Of

Eosinophils are important to the pathogenesis of allergic asthma, and are increased in bronchoalveolar lavage within four hours after bronchoprovocation of allergic asthmatic patients, and remain significantly increased up to 24 hours later. While the components of human eosinophil granules have been recently isolated and purified, the mechanisms of degranulation have yet to be elucidated.We obtained blood from two volunteers who had a history of allergic rhinitis and asthma and a positive skin test (5x5mm wheal) to Alternaria and Ragweed. Eosinophils were obtained using a modification of the method described by Roberts and Gallin.

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Expression Level of MiRNA-126 in Serum Exosomes of Allergic Asthma Patients and Lung Tissues of Asthmatic Mice

Current Drug Metabolism ◽

10.2174/1389200220666191011114452 ◽

2019 ◽

Vol 20 (10) ◽

pp. 799-803 ◽

Cited By ~ 2

Author(s):

Meizhen Zhao ◽

Yu-Pei Li ◽

Xiao-Rui Geng ◽

Miao Zhao ◽

Shi-Bo Ma ◽

...

Keyword(s):

Allergic Asthma ◽

Real Time ◽

Real Time Pcr ◽

Lavage Fluid ◽

Asthmatic Patients ◽

Protein Levels ◽

Sige Level ◽

Bronchial Lumen ◽

Asthma Patients ◽

Serum Exosomes

Background: To investigate MiRNA-126 amounts in serum exosomes from allergic asthma patients as well as lung tissues of asthmatic mice, evaluating the expression of its target gene DNMT1 in mouse specimens. Methods: MiRNA-126 amounts in serum exosomes from asthmatic patients were detected by real-time PCR. The mouse model of allergic asthma was established by OVA-sensitization, and allergic symptoms were recorded; serum IL-4 and sIgE level evaluation (ELISA), broncho alveolar lavage fluid (BALF) cell count and H&E staining were performed to assess airway inflammation. MiRNA-126 and DNMT1 levels in the lung of asthmatic and control mice were detected by real-time PCR; DNMT1 protein levels were detected by immunoblot. Results: MiRNA-126 amounts in peripheral blood exosomes from patients with allergic asthma were significantly higher than that of healthy volunteers (P<0.05). The frequencies of scratching of both sides of the nose and sneezing were elevated within 10 min of excitation in asthmatic rats compared with controls. Meanwhile, OVA-sIgE and IL-4 levels were significantly higher in asthmatic animals than controls (P<0.05). In the asthma group, narrowed bronchial lumen and thickened wall were observed, and bronchial and peripheral vessels showed overt inflammatory cell infiltration. Eosinophil, neutrophil and mast cell amounts in the BALF of asthmatic mice were significantly higher than control values. Furthermore, lung miRNA-126 expression in asthmatic mice was significantly higher than that of controls. Finally, DNMT1 mRNA and protein levels were significantly lower in asthmatic animals compared with controls (P < 0.01). Conclusion: MiRNA-126 is highly expressed in serum exosomes from allergic asthma patients and lung tissues of asthmatic mice, suggesting that it may be involved in the pathogenesis of bronchial asthma.

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Increased presence of nuclear DNAJA3 and upregulation of cytosolic STAT1 and of nucleic acid sensors trigger innate immunity in the ClpP-null mouse

Neurogenetics ◽

10.1007/s10048-021-00657-2 ◽

2021 ◽

Author(s):

Antonia Maletzko ◽

Jana Key ◽

Ilka Wittig ◽

Suzana Gispert ◽

Gabriele Koepf ◽

...

Keyword(s):

Innate Immunity ◽

Nucleic Acid ◽

Inflammatory Responses ◽

Subcellular Fractionation ◽

Inflammatory Factors ◽

Null Mouse ◽

Loss Of Function ◽

Response Factors ◽

Perrault Syndrome ◽

Acid Sensors

AbstractMitochondrial dysfunction may activate innate immunity, e.g. upon abnormal handling of mitochondrial DNA in TFAM mutants or in altered mitophagy. Recent reports showed that also deletion of mitochondrial matrix peptidase ClpP in mice triggers transcriptional upregulation of inflammatory factors. Here, we studied ClpP-null mouse brain at two ages and mouse embryonal fibroblasts, to identify which signaling pathways are responsible, employing mass spectrometry, subcellular fractionation, immunoblots, and reverse transcriptase polymerase chain reaction. Several mitochondrial unfolded protein response factors showed accumulation and altered migration in blue-native gels, prominently the co-chaperone DNAJA3. Its mitochondrial dysregulation increased also its extra-mitochondrial abundance in the nucleus, a relevant observation given that DNAJA3 modulates innate immunity. Similar observations were made for STAT1, a putative DNAJA3 interactor. Elevated expression was observed not only for the transcription factors Stat1/2, but also for two interferon-stimulated genes (Ifi44, Gbp3). Inflammatory responses were strongest for the RLR pattern recognition receptors (Ddx58, Ifih1, Oasl2, Trim25) and several cytosolic nucleic acid sensors (Ifit1, Ifit3, Oas1b, Ifi204, Mnda). The consistent dysregulation of these factors from an early age might influence also human Perrault syndrome, where ClpP loss-of-function leads to early infertility and deafness, with subsequent widespread neurodegeneration.

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Luteolin transforms the polarity of bone marrow-derived macrophages to regulate the cytokine storm

Journal of Inflammation ◽

10.1186/s12950-021-00285-5 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Shuxia Wang ◽

Shuhang Xu ◽

Jing Zhou ◽

Li Zhang ◽

Xiaodong Mao ◽

...

Keyword(s):

Bone Marrow ◽

Inflammatory Responses ◽

Bone Marrow Cells ◽

Membrane Surface ◽

Inflammatory Factors ◽

Mouse Bone Marrow ◽

Macrophage Polarisation ◽

Ifn Γ ◽

Anti Inflammatory ◽

M1 Type

Abstract Background Macrophages are indispensable regulators of inflammatory responses. Macrophage polarisation and their secreted inflammatory factors have an association with the outcome of inflammation. Luteolin, a flavonoid abundant in plants, has anti-inflammatory activity, but whether luteolin can manipulate M1/M2 polarisation of bone marrow-derived macrophages (BMDMs) to suppress inflammation is still unclear. This study aimed to observe the effects of luteolin on the polarity of BMDMs derived from C57BL/6 mice and the expression of inflammatory factors, to explore the mechanism by which luteolin regulates the BMDM polarity. Methods M1-polarised BMDMs were induced by lipopolysaccharide (LPS) + interferon (IFN)-γ and M2-polarisation were stimulated with interleukin (IL)-4. BMDM morphology and phagocytosis were observed by laser confocal microscopy; levels of BMDM differentiation and cluster of differentiation (CD)11c or CD206 on the membrane surface were assessed by flow cytometry (FCM); mRNA and protein levels of M1/M2-type inflammatory factors were performed by qPCR and ELISA, respectively; and the expression of p-STAT1 and p-STAT6 protein pathways was detected by Western-blotting. Results The isolated mouse bone marrow cells were successfully differentiated into BMDMs, LPS + IFN-γ induced BMDM M1-phenotype polarisation, and IL-4 induced M2-phenotype polarisation. After M1-polarised BMDMs were treated with luteolin, the phagocytosis of M1-polarized BMDMs was reduced, and the M1-type pro-inflammatory factors including IL-6, tumour necrosis factor (TNF)-α, inducible nitric oxide synthase (iNOS), and CD86 were downregulated while the M2-type anti-inflammatory factors including IL-10, IL-13, found in inflammatory zone (FIZZ)1, Arginase (Arg)1 and CD206 were upregulated. Additionally, the expression of M1-type surface marker CD11c decreased. Nevertheless, the M2-type marker CD206 increased; and the levels of inflammatory signalling proteins phosphorylated signal transducer and activator of transcription (p-STAT)1 and p-STAT6 were attenuated and enhanced, respectively. Conclusions Our study suggests that luteolin may transform BMDM polarity through p-STAT1/6 to regulate the expression of inflammatory mediators, thereby inhibiting inflammation. Naturally occurring luteolin holds promise as an anti-inflammatory and immunomodulatory agent.

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