Severe Vitamin E deficiency modulates airway allergic inflammatory responses in the murine asthma model

Lim, Yunsook; Vasu, Vihas T.; Valacchi, Giuseppe; Leonard, Scott W.; Aung, Hnin Hnin; Schock, Bettina; Kenyon, Nicholas J.; Li, Chin‐Shang; Traber, Maret G.; Cross, Carroll E.

doi:10.1080/10715760801976600

Cited by 25 publications

(23 citation statements)

References 63 publications

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“…In a recent study, a systematically review revealed the associations between inflammatory responses and asthma severity in pediatric asthma, which indicated that IFN-γ, IL-10 and IL-17 may serve as prognostic indicators of pediatric asthma (34). In addition, various strategies targeting inflammatory responses to improve airway remodeling in asthma physiopathology have been investigated, and the results of these studies support the hypothesis that modulating the allergic inflammation improved asthma physiopathology in patients with asthma in animals model and clinical trials (35)(36)(37)(38). Furthermore, previous reports have indicated that the pathogenesis of airway inflammation in asthma patients may be associated with the normal function and maintenance of the airway smooth muscle cells (39)(40)(41).…”

Section: Discussionsupporting

confidence: 52%

Clinical efficacy of recombinant human latrophilin 3 antibody in the treatment of pediatric asthma

Liu¹,

Zhang²,

Liu³

2017

Exp Ther Med

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Abstract. Pediatric asthma is a chronic pulmonary inflammatory disease featuring hypersecretion of mucus and inflammation in the airway, resulting in dysfunction of the airway smooth muscle. Previous evidence demonstrated that latrophilins, a novel family of receptors, present a beneficial effect on airway smooth muscle cells. In the present study, the therapeutic effects of recombinant human latrophilin 3 (rhLPHN3) antibody (Ab) in patients with pediatric asthma were investigated, and the molecular mechanism underlying the function of LPHN3 in the treatment of asthma in clinical practice was examined. A total of 342 pediatric asthma cases were recruited and randomly divided into three groups, receiving treatment with rhLPHN3 Ab (n=134), salbutamol (n=108) or montelukast (n=100) by nasal aerosolization. Each group received the respective clinically tested dose for 16 weeks. Inflammatory factors interleukin (IL)-10, IL-17, IL-4, matrix metallopeptidase-9 (MMP-9), interferon-γ (IFN-γ) and transforming growth factor-β (TGF-β) levels in peripheral blood mononuclear cells were analyzed prior to and post treatment. The clinical outcomes revealed that pathological alterations were significantly improved following treatment with rhLPHN3 Ab for patients with pediatric asthma when compared with those receiving salbutamol and montelukast. It was also observed that rhLPHN3 Ab downregulated the plasma concentration levels of IL-10, IL-17, IL-4 and MMP-9, and upregulated IFN-γ and TGF-β levels in the three groups. In addition, clinical data demonstrated that rhLPHN3 Ab significantly promoted E-selectin and mucin 5AC expression, as well as improved the activation of nuclear factor (NF)-κB p65 DNA binding activity and the phosphorylation levels of protein kinase A. Furthermore, rhLPHN3 Ab markedly improved adhesion and proliferation of airway smooth muscle cells, which led to promotion of the contraction of these cells.In conclusion, these clinical data suggest that rhLPHN3 Ab serves an important role in the inhibition of inflammatory mediators through downregulation of NF-κB signaling pathway, which contributes to airway remodeling and bronchodilation in patients with pediatric asthma.

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Section: Discussionsupporting

confidence: 52%

Clinical efficacy of recombinant human latrophilin 3 antibody in the treatment of pediatric asthma

Liu¹,

Zhang²,

Liu³

2017

Exp Ther Med

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“…Our interpretation of this study is that high g-tocopherol in the soy oil negated the effect of the a-tocopherol that was administered. Mice deficient in liver a-tocopherol transfer protein (aTTP) exhibit severe deficiency in tissue a-and g-tocopherol as well as reduced IgE after OVA challenge to the lung (35). In these mice, it is not known whether severe tocopherol deficiency during mouse development alters leukocyte hematopoiesis or leukocyte responsiveness.…”

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confidence: 99%

Two Faces of Vitamin E in the Lung

Cook‐Mills

Abdala-Valencia

Hartert

2013

Am J Respir Crit Care Med

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Asthma and allergic lung disease occur as complex environmental and genetic interactions. Clinical studies of asthma indicate a number of protective dietary factors, such as vitamin E, on asthma risk. However, these studies have had seemingly conflicting outcomes. In this perspective, we discuss opposing regulatory effects of tocopherol isoforms of vitamin E, mechanisms for tocopherol isoform regulation of allergic lung inflammation, association of vitamin E isoforms with outcomes in clinical studies, and how the variation in global prevalence of asthma may be explained, at least in part, by vitamin E isoforms.Keywords: asthma; a-tocopherol; g-tocopherol; human; mouse Asthma and allergic lung disease occur as complex environmental and genetic interactions (1). The World Health Organization has reported that the prevalence of asthma from 1950 to the present has increased in many countries, including countries with high rates of asthma, intermediate rates of asthma, or low rates of asthma (2-4). The marked differences in rates of asthma within countries, in migrating populations, and over relatively short periods of time support an important role of the local environment, such as diet, in asthma inception. Prospective epidemiological studies, observational cross-sectional studies, and some randomized prevention trials have demonstrated the impact of a number of protective dietary factors, such as vitamin E, on asthma risk. However, these studies have had seemingly conflicting outcomes. We need to determine why there are low rates of allergic disease in developing countries and better understand the differences in diet and lifestyle that may really underpin allergic disease. One environmental change over the past 40 years has been an increase in the g-tocopherol isoform of vitamin E in the diet and in infant formulas (5, 6). We recently demonstrated that g-tocopherol increases allergic lung inflammation in mice (6)(7)(8). In this perspective, we discuss why we have yet to uncover the complex and potentially protective effects of isoforms of vitamin E on asthma in humans and in animal models of lung inflammation. We also review mechanisms for tocopherol isoform regulation of allergic lung inflammation in animals and discuss how the variation in global prevalence of asthma may be explained, at least in part, by country-specific plasma g-tocopherol differences.Vitamin E consists of natural isoforms and synthetic racemic isoforms. The eight natural isomers are d-a-, d-b-, d-g-, d-d-tocopherol and d-a-, d-b-, d-g-, d-d-tocotrienol. Plants synthesize the natural isoforms from tyrosine and chlorophyll (9). Then, these tocols are consumed in the diet from plant lipids. Mammals do not interconvert the tocopherol isoforms. The most abundant isoforms are a-tocopherol and g-tocopherol, which differ by one methyl group ( Figure 1A). There are approximately 10-fold higher tissue concentrations of a-tocopherol than g-tocopherol due to preferential transfer of a-tocopherol in the liver by a-tocopherol transfer protein and due to ...

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“…Animal diet and water were provided ad libitum. Allergic asthma sensitization was performed as previously reported in work by Kenyon and colleagues [26,27]. Briefly, mice (6-8 weeks of age) were sensitized via intraperitoneal injection (i.p.)…”

Section: Animals Sensitization and Particle Administrationmentioning

confidence: 99%

“…We have used an ovalbumin sensitization and exposure mouse model of allergic airway inflammation to determine the lung retention and biodistribution of polystyrene nanoparticles (∼100 nm) and compared results to a normal mouse control group. The ovalbumin mouse model is well established in the literature and is commonly used to study asthma [17,26,27]. This model has proven to exhibit key features of asthma, including airway hyperresponsiveness, eosinophilic bronchitis, acute inflammation, increased airway reactivity, and mild airway obstruction [26].…”

Section: Introductionmentioning

confidence: 99%

Tracking retention and transport of ultrafine polystyrene in an asthmatic mouse model using positron emission tomography

Enright

Bratt

Bluhm

et al. 2013

Experimental Lung Research

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Upon exposure to particulates, asthmatic individuals are more susceptible to deleterious health effects and increased morbidity and mortality when compared to healthy individuals. These effects are not limited to the respiratory system; increases in acute cardiovascular events have been observed. The development of extrapulmonary illnesses has led to interest in determining whether particles move out of the lungs and whether transport of particles differs for asthmatic individuals. Differences in particle deposition and retention in asthmatic versus normal subjects have been explored in the literature using the gamma camera, a two-dimensional imaging technique. Herein we report the deposition and fate of (64)Cu-labeled 100 nm polystyrene particles in a mouse model of asthma using positron emission tomography (PET). All animals were handled humanely under an approved protocol (UC Davis Institutional Animal Care and Use Committee). Particles were administered by intratracheal instillation and animals were imaged over 48 hours using PET. Biodistribution was determined from images using Regions of Interest (ROI) analysis. After 48 hours, for the asthmatic animals, we observed that ~28% of the initial dose is cleared from the lungs; particle accumulation in small amounts is evident in the GI (gastrointestinal) tract, liver, and bladder. This decrease in lung retention is significantly different when compared to the normal mouse (~11%DD), which showed minimal particle transport out of the lung (P < 0.001). This study indicates that ultrafine particles (UFP) undergo enhanced transport out of the lungs in an asthma model. This observed transport may facilitate the adverse peripheral effects associated with particulate exposure.

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Severe Vitamin E deficiency modulates airway allergic inflammatory responses in the murine asthma model

Cited by 25 publications

References 63 publications

Clinical efficacy of recombinant human latrophilin 3 antibody in the treatment of pediatric asthma

Clinical efficacy of recombinant human latrophilin 3 antibody in the treatment of pediatric asthma

Two Faces of Vitamin E in the Lung

Tracking retention and transport of ultrafine polystyrene in an asthmatic mouse model using positron emission tomography

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