Sesame Oil Attenuates Ovalbumin-Induced Pulmonary Edema and Bronchial Neutrophilic Inflammation in Mice

Background. Allergic asthma is one of the most common chronic inflammatory diseases of airways. Severe asthma may lead to hospitalization and death. Sesame oil is a natural product with anti-inflammatory property. However, the effect of sesame oil on allergic asthma has never been studied.Objective. We investigate the effect of sesame oil on pulmonary inflammation in allergic asthma model.Methods. Allergic airway inflammation was induced by sensitizing with two doses of 10 mg ovalbumin (OVA) and then challenged with 1% OVA nebulizer exposure (1 h/day) for 3 days. Sesame oil (0.25, 0.5, or 1 mL/kg/day) was given orally 30 min before each challenge. Samples were collected 24 h after the last challenge.Results. Data showed that sesame oil inhibited pulmonary edema and decreased interleukin (IL)-1βand IL-6 levels in bronchoalveolar lavage fluid in OVA-treated mice. Sesame oil also decreased pulmonary nitrite level, inducible nitric oxide synthase expression, and neutrophil infiltration induced by OVA. Further, sesame oil decreased serum IgE level in OVA-treated mice.Conclusion. Sesame oil may attenuate pulmonary edema and bronchial neutrophilic inflammation by inhibiting systemic IgE level in allergic asthma.

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Bacillus clausii, a Foreshore-Derived Probiotic, Attenuates Allergic Airway Inflammation Through Downregulation of Hypoxia Signaling

Journal of Rhinology ◽

10.18787/jr.2020.00325 ◽

2020 ◽

Vol 27 (2) ◽

pp. 108-116

Author(s):

Hyelim Park ◽

Ah-Yeoun Jung ◽

Chung-Soon Chang ◽

Young Hyo Kim

Keyword(s):

Pulmonary Inflammation ◽

Allergic Airway Inflammation ◽

Lung Parenchyma ◽

Airway Disease ◽

Lavage Fluid ◽

Specific Ige ◽

Allergic Airway Disease ◽

Eosinophil Infiltration ◽

Bacillus Clausii ◽

Lung Histopathology

Background and Objectives: The immunomodulatory effects and mechanism of probiotics in allergic airway disease are largely unknown. We studied whether Bacillus clausii (BC), a probiotic derived from mudflats, had anti-allergic effects and compared the results with those of Lactobacillus paracasei (LP). We also examined whether the anti-allergic mechanisms of probiotics are associated with hypoxia signaling.Materials and Method: Forty-two BALB/c mice were randomly assigned to six experimental groups: controls, ovalbumin (OVA)-induced mice for inducing asthma, and OVA-induced mice that were orally administered LP or BC, at 1×109 or 5×109 CFU/mL each. We performed differential cell count testing on bronchoalveolar lavage fluid (BALF), lung histopathology, serum totals and OVA-specific IgE and IgG1 assessments, Th2 cytokine titers (IL-4, IL-5) in BALF and pulmonary parenchyma, quantitative PCR for heme oxygenase (HO)-1 and Hif-1α, and immunohistochemistry.Results: Compared to the OVA group mice, OVA-sensitized mice treated with LP or BC showed significantly reduced numbers of eosinophils and neutrophils in the BALF (p<0.05). Both probiotics also significantly reduced pulmonary inflammation and eosinophil infiltration. Mice in the LP or BC group had a substantially lower titer of IL-4 and IL-5 in BALF, and decreased IL-4 and IL-5 expression in the lung parenchyma. Real-time PCR and immunohistochemistry showed that both LP and BC could significantly suppress HO-1 and Hif-1α expression in asthmatic mice (p<0.05).Conclusion: BC can attenuate murine allergic asthma by regulating HIF-1α signaling, and its anti-allergic effect is comparable to that of LP.

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Changes in Pulmonary Function and Parasite Burden in Rats Infected with Strongyloides venezuelensis Concomitant with Induction of Allergic Airway Inflammation

Infection and Immunity ◽

10.1128/iai.71.5.2607-2614.2003 ◽

2003 ◽

Vol 71 (5) ◽

pp. 2607-2614 ◽

Cited By ~ 39

Author(s):

Deborah Negrão-Corrêa ◽

Micheline R. Silveira ◽

Cynthia M. Borges ◽

Danielle G. Souza ◽

Mauro M. Teixeira

Keyword(s):

Airway Inflammation ◽

Mutual Influence ◽

Pulmonary Inflammation ◽

Allergic Airway Inflammation ◽

Parasite Burden ◽

Allergic Diseases ◽

Lavage Fluid ◽

Eosinophil Infiltration ◽

Asthmatic Patients ◽

Strongyloides Venezuelensis

ABSTRACT The prevalence of allergic diseases such as asthma has increased markedly over the past few decades. To evaluate the possible mutual influence of helminth infection and allergy, the combined effects of experimental allergic airway inflammation and infection with Strongyloides venezuelensis on various parasitological and inflammatory indices were evaluated in the rat. A challenge of immunized rats with aerosolized ovalbumin (OVA) resulted in eosinophilic inflammation that peaked 48 h after the challenge and was accompanied by airway hyperresponsiveness (AHR) to an intravenous acetylcholine challenge. S. venezuelensis infection concomitant with an OVA challenge of immunized rats resulted in prolonged pulmonary inflammation with increased eosinophil infiltration in bronchoalveolar lavage fluid but not in the lung tissue. These rats also showed a significant parasite burden reduction, especially during parasite migration through the lungs. However, the fecundity rates of worms that reached the intestine were similar in allergic and nonallergic animals. Despite airway inflammation, the increased responsiveness of the airways in the experimental asthma model was suppressed during parasite migration through the lungs (2 days). In contrast, parasite-induced AHR was unchanged 5 days after infection in immunized and challenged rats. In conclusion, infection with S. venezuelensis interfered with the onset of AHR following an antigen challenge of immunized rats. The ability of parasites to switch off functional airway responses is therapeutically relevant because we may learn from parasites how to modulate lung function and, hence, the AHR characteristic of asthmatic patients.

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Down-regulation of miR-let-7e attenuates LPS-induced acute lung injury in mice via inhibiting pulmonary inflammation by targeting SCOS1/NF-κB pathway

Bioscience Reports ◽

10.1042/bsr20201089 ◽

2021 ◽

Vol 41 (1) ◽

Author(s):

Wuquan Li ◽

Wentao Zhang ◽

Jun Liu ◽

Yalong Han ◽

He Jiang ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Inflammatory Response ◽

Inflammatory Diseases ◽

Pulmonary Inflammation ◽

Lavage Fluid ◽

Luciferase Reporter ◽

Cytokine Signaling ◽

Down Regulation ◽

Reporter Assays

Abstract Excessive pulmonary inflammatory response is critical in the development of acute lung injury (ALI). Previously, microRNAs (miRNAs) have been recognized as an important regulator of inflammation in various diseases. However, the effects and mechanisms of miRNAs on inflammatory response in ALI remain unclear. Herein, we tried to screen miRNAs in the processes of ALI and elucidate the potential mechanism. Using a microarray assay, microRNA let-7e (let-7e) was chose as our target for its reported suppressive roles in several inflammatory diseases. Down-regulation of let-7e by antagomiR-let-7e injection attenuated LPS-induced acute lung injury. We also found that antagomiR-let-7e could obviously improve the survival rate in ALI mice. Moreover, antagomiR-let-7e treatment reduced the production of proinflammatory cytokines (i.e., TNF-α, IL-1β and IL-6) in bronchoalveolar lavage fluid (BALF) of LPS-induced ALI mice. Luciferase reporter assays confirmed that suppressor of cytokine signaling 1 (SOCS1), a powerful attenuator of nuclear factor kappa B (NF-κB) signaling pathway, was directly targeted and suppressed by let-7e in RAW264.7 cells. In addition, it was further observed that SOCS1 was down-regulated, and inversely correlated with let-7e expression levels in lung tissues of ALI mice. Finally, down-regulation of let-7e suppressed the activation of NF-κB pathway, as evidenced by the reduction of p-IκBα, and nuclear p-p65 expressions in ALI mice. Collectively, our findings indicate that let-7e antagomir protects mice against LPS-induced lung injury via repressing the pulmonary inflammation though regulation of SOCS1/NF-κB pathway, and let-7e may act as a potential therapeutic target for ALI.

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Attenuation of pulmonary injury by an inhaled MMP inhibitor in the endotoxin lung injury model

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00420.2019 ◽

2020 ◽

Vol 319 (6) ◽

pp. L1036-L1047

Author(s):

Adam Gerber ◽

Monica Goldklang ◽

Kyle Stearns ◽

Xinran Ma ◽

Rui Xiao ◽

...

Keyword(s):

Lung Injury ◽

Pulmonary Edema ◽

Pulmonary Inflammation ◽

Neutrophil Migration ◽

Neutrophil Infiltration ◽

Vascular Integrity ◽

Pulmonary Vascular Permeability ◽

Mmp Inhibitor ◽

Cell Counts ◽

Lung Injury Model

Acute respiratory distress syndrome (ARDS) is characterized by pulmonary edema and poor gas exchange resulting from severe inflammatory lung injury. Neutrophilic infiltration and increased pulmonary vascular permeability are hallmarks of early ARDS and precipitate a self-perpetuating cascade of inflammatory signaling. The biochemical processes initiating these events remain unclear. Typically associated with extracellular matrix degradation, recent data suggest matrix metalloproteinases (MMPs) are regulators of pulmonary inflammation. To demonstrate that inhalation of a broad MMP inhibitor attenuates LPS induced pulmonary inflammation. Nebulized CGS27023AM (CGS) was administered to LPS-injured mice. Pulmonary CGS levels were examined by mass spectroscopy. Inflammatory scoring of hematoxylin-eosin sections, examination of vascular integrity via lung wet/dry and bronchoalveolar lvage/serum FITC-albumin ratios were performed. Cleaved caspase-3 levels were also assessed. Differential cell counts and pulse-chase labeling were utilized to determine the effects of CGS on neutrophil migration. The effects of CGS on human neutrophil migration and viability were examined using Boyden chambers and MTT assays. Nebulization successfully delivered CGS to the lungs. Treatment decreased pulmonary inflammatory scores, edema, and apoptosis in LPS treated animals. Neutrophil chemotaxis was reduced by CGS treatment, with inhalation causing significant reductions in both the total number and newly produced bromodeoxyuridine-positive cells infiltrating the lung. Mechanistic studies on cells isolated from humans demonstrate that CGS-treated neutrophils exhibit decreased chemotaxis. The protective effect observed following treatment with a nonspecific MMP inhibitor indicates that one or more MMPs mediate the development of pulmonary edema and neutrophil infiltration in response to LPS injury. In accordance with this, inhaled MMP inhibitors warrant further study as a potential new therapeutic avenue for treatment of acute lung injury.

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Pulmonary inflammation induced by high-stretch ventilation is mediated by tumor necrosis factor signaling in mice

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00304.2004 ◽

2005 ◽

Vol 288 (4) ◽

pp. L599-L607 ◽

Cited By ~ 60

Author(s):

Michael R. Wilson ◽

Sharmila Choudhury ◽

Masao Takata

Keyword(s):

Lung Injury ◽

Pulmonary Inflammation ◽

Biological Significance ◽

Blood Gases ◽

Neutrophil Infiltration ◽

Lavage Fluid ◽

Lung Lavage ◽

Lung Mechanics ◽

Wild Type ◽

Double Knockout

Although high-stretch mechanical ventilation has been demonstrated to induce lung inflammation, the roles of soluble mediators, in particular TNF, remain controversial. We have previously shown in mice that high-stretch ventilation, in the absence of preceding lung injury, induces expression of bioactive TNF in lung lavage fluid early in the course of injury, but the biological significance of this, if any, has yet to be determined. We therefore investigated the pulmonary inflammatory response to a transient period of high-stretch ventilation in anesthetized mice lacking TNF receptors and mice treated with anti-TNF antibodies. A standardized stretch-induced lung injury (assessed by lung mechanics, blood gases, and lavage protein content), followed by noninjurious low-stretch ventilation for 3 h, produced significant alveolar neutrophil infiltration in wild-type mice. However, neutrophil recruitment was substantially attenuated in TNF receptor double knockout mice and in wild-type mice treated with intratracheal anti-TNF antibody. This attenuation was not associated with decreased concentrations of neutrophil attractant CXC chemokines (macrophage inflammatory protein-2 and keratinocyte-derived chemokine) in lavage fluid. In contrast to intratracheal antibody, intravenous anti-TNF antibody did not reduce neutrophil infiltration, suggesting that the role of TNF signaling is localized within the alveolar space and does not require decompartmentalization of TNF into the circulation. These findings provide the first direct evidence that pulmonary inflammation induced by high-stretch ventilation without underlying lung injury possesses a significant TNF-dependent component. The results suggest a potential for regional anti-TNF treatment in attenuating stretch-induced pulmonary inflammation.

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Carica papaya Leaf Extract modulates mRNA expression of Aquaporins in Mouse Model of Allergic Airway Inflammation

10.53350/pjmhs2115102512 ◽

2021 ◽

Vol 15 (10) ◽

pp. 2512-2515

Author(s):

Asma Inam ◽

Muhammad Sair ◽

Sadia Ikram ◽

Sadia Majeed ◽

Gul-E- Nazish ◽

...

Keyword(s):

Body Weight ◽

Mouse Model ◽

Pulmonary Edema ◽

Mrna Expression ◽

Airway Inflammation ◽

Allergic Asthma ◽

Leaf Extract ◽

Carica Papaya ◽

Allergic Airway Inflammation ◽

Th2 Cytokines

Background: Asthma is a chronic inflammatory disease affecting smaller airways. Airflow obstruction leading to airway hyper-responsiveness and increased mucus production are salient features of asthma pathophysiology. Generally, Th2 cytokines are increased in allergic asthma. Aim: To propose the molecular mechanisms by which Carica Papaya Leaves Extract (CPLE) alleviates pulmonary edema in animal model of allergic airway inflammation comparable to methylprednisolone. Place and duration of study: Pharmacology Department, University of Health Sciences Lahore for 1 year. Methods: We took twenty four male BALB/c mice and divided them equally into four groups. The control group was given PBS only, while Group II served as diseased group and induced airway inflammation by ovalbumin. Group III and IV were first induced with airway inflammation and side by side treated with Carica papaya leaf extract (CPLE) 100mg/kg body weight orally and methylprednisolone 15 mg/kg body weight intraperitoneally for seven consecutive days respectively. At the end of the experimental protocol, mice were euthanized and lung wet/dry ratio was measured. mRNA expression of AQP1 and AQP5 in lung tissue were also determined using RT-PCR. Results: Ethanolic extract of Carica Papaya leaves decreased all markers of pulmonary edema in mouse model of allergic airway inflammation comparable to methylprednisolone by decreasing lung wet/dry ratio and enhancing AQP1 and AQP5 mRNA expression. Conclusion: Carica Papaya leaves extract may diminish pulmonary edema in mice associated with allergic asthma. Keywords: AQP1, AQP5 (Aquaporins), Carica Papaya Leaves Extract (CPLE), Pulmonary Edema, Th2 cytokines.

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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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Obesity-Induced Dysbiosis Exacerbates IFN-γ Production and Pulmonary Inflammation in the Mycobacterium tuberculosis Infection

Cells ◽

10.3390/cells10071732 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1732

Author(s):

Sandra Patricia Palma Albornoz ◽

Thais Fernanda de Campos Fraga-Silva ◽

Ana Flávia Gembre ◽

Rômulo Silva de Oliveira ◽

Fernanda Mesquita de Souza ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Gut Microbiota ◽

Inflammatory Diseases ◽

Pulmonary Inflammation ◽

Host Susceptibility ◽

Chronic Infections ◽

Mycobacterium Tuberculosis Infection ◽

Pulmonary Damage ◽

Ifn Γ

The microbiota of the gut–lung axis affects local and far-reaching immune responses and might also trigger chronic and inflammatory diseases. We hypothesized that gut dysbiosis induced by obesity, which coexists in countries with a high tuberculosis burden, aggravates the host susceptibility and the pulmonary damage tolerance. To assess our hypothesis, we used a model of high-fat diet (HFD)-induced obesity, followed by infection of C57BL/6 mice with Mycobacterium tuberculosis. We showed that obesity increased the susceptibility, the pulmonary inflammation and IFN-γ levels in M. tuberculosis-infected mice. During the comorbidity obesity and tuberculosis, there is an increase of Bacteroidetes and Firmicutes in the lungs, and an increase of Firmicutes and butyrate in the feces. Depletion of gut microbiota by antibiotic treatment in the obese infected mice reduced the frequencies of CD4+IFN-γ+IL-17− cells and IFN-γ levels in the lungs, associated with an increase of Lactobacillus. Our findings reinforce the role of the gut–lung axis in chronic infections and suggest that the gut microbiota modulation may be a potential host-directed therapy as an adjuvant to treat TB in the context of IFN-γ-mediated immunopathology.

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

Allergy Asthma & Clinical Immunology ◽

10.1186/s13223-021-00534-5 ◽

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

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A role for bronchial epithelial autotaxin in ventilator-induced lung injury

Intensive Care Medicine Experimental ◽

10.1186/s40635-021-00379-7 ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

Ioanna Nikitopoulou ◽

Ioanna Ninou ◽

Nikolaos Manitsopoulos ◽

Ioanna Dimopoulou ◽

Stylianos E. Orfanos ◽

...

Keyword(s):

Lung Injury ◽

Protein Concentration ◽

Bronchoalveolar Lavage Fluid ◽

Pulmonary Inflammation ◽

Small Animal ◽

Lavage Fluid ◽

Bronchial Epithelial ◽

Ventilator Induced Lung Injury ◽

Lung Histopathology ◽

Genetic Deletion

Abstract Background The pathophysiology of acute respiratory distress syndrome (ARDS) may eventually result in heterogeneous lung collapse and edema-flooded airways, predisposing the lung to progressive tissue damage known as ventilator-induced lung injury (VILI). Autotaxin (ATX; ENPP2), the enzyme largely responsible for extracellular lysophosphatidic acid (LPA) production, has been suggested to play a pathogenic role in, among others, pulmonary inflammation and fibrosis. Methods C57BL/6 mice were subjected to low and high tidal volume mechanical ventilation using a small animal ventilator: respiratory mechanics were evaluated, and plasma and bronchoalveolar lavage fluid (BALF) samples were obtained. Total protein concentration was determined, and lung histopathology was further performed Results Injurious ventilation resulted in increased BALF levels of ATX. Genetic deletion of ATX from bronchial epithelial cells attenuated VILI-induced pulmonary edema. Conclusion ATX participates in VILI pathogenesis.

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