Thymic Stromal Lymphopoietin Neutralization Inhibits the Immune Adjuvant Effect of Di-(2-Ethylhexyl) Phthalate in Balb/c Mouse Asthma Model

You, Huihui; Li, Rui; Wei, Chenxi; Chen, Shaohui; Mao, Lin; Zhang, Zhenye; Yang, Xu

doi:10.1371/journal.pone.0159479

Cited by 22 publications

(12 citation statements)

References 49 publications

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“…In contrast, in our hands abrogation of the effects of all three alarmins did not influence local mucus production, epithelial metaplasia, collagen laydown and eotaxin expression in the airways, whereas only abrogation of IL‐33 signalling affected airways hypersensitivity to methacholine, suggesting that this is the total extent of the contribution of the alarmins to this phenomenon, as least insofar as it reflects short‐term changes in the airways in our model. Similarly, a recent study using a similar murine model suggested that deletion of the TSLP receptor does not abrogate airways epithelial metaplasia and mucus secretion . Another recent study using a similar model suggests that IL‐25 blockade abrogates airways hyperresponsiveness employed a higher concentration of anti‐IL‐25 antibody than in the present study, and the possible contribution of altered mucus production to this effect was not specifically addressed.…”

Section: Discussioncontrasting

confidence: 57%

“…Previous studies suggest significant roles for CTGF, FGFR4, fibronectin and MMP in the pathogenesis of asthma, most likely by participating in the mechanisms of deposition of extracellular matrix and local fibrosis . Using a similar murine model we previously reported that deletion of the St2 gene significantly inhibits the expression of these molecules .…”

Section: Discussionmentioning

confidence: 75%

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Combined blockade of IL‐25, IL‐33 and TSLP mediates amplified inhibition of airway inflammation and remodelling in a murine model of asthma

Wang

Zhang

et al. 2019

Respirology

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Background and objective: Isolated blockade of IL-25, IL-33 and thymic stromal lymphopoietin (TSLP) has been shown to reduce airways inflammation and hyperresponsiveness in murine asthma model. The hypothesis that combined blockade of all three cytokines can accomplish this more effectively has never been addressed. Methods: We studied a murine asthma model employing sensitization and challenge with ovalbumin (OVA) or saline control. To discern the effects of IL-33 blockade, we compared outcomes in strain identical, wild-type and IL-33 receptor (St2 −/− ) gene-deleted mice. We then examined, in the St2 −/− animals, the effects of additional, single or combined blockade of IL-25 and TSLP with blocking antibodies. Outcomes included airways reactivity, inflammatory cellular infiltration, epithelial cell metaplasia, deposition of fibrosis-related proteins, local Th2-type cytokine expression and total and specific serum IgE concentrations measured by ELISA and quantitative immunohistochemistry. Results: St2 −/− gene deletion significantly reduced airways reactivity, inflammatory cellular infiltration, lung tissue expression of Th2 cytokines and fibrosis related proteins and serum total IgE in response to OVA sensitization and challenge. Additional administration of anti-IL-25 and anti-TSLP blocking antibodies to the St2 −/− mice further significantly reduced inflammation, Th2 cytokine expression, airways fibrosis and IgE production, while anti-TSLP alone reduced eosinophil infiltration and local IL-4 expression. The airways inflammatory cellular infiltrate and lung tissue expression of Th2 cytokine, but not fibrosis-related proteins were also reduced in the presence of isotype identical, control antibodies.Conclusion: Combined blockade of these three cytokines may better ameliorate airways pathological changes in this murine asthma model, with implications for human asthma. SUMMARY AT A GLANCECombined blockade of IL-25, IL-33 and TSLP may augment disease control and further reduce airways inflammation and remodelling in chronic asthma.

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Section: Discussioncontrasting

confidence: 57%

Section: Discussionmentioning

confidence: 75%

Combined blockade of IL‐25, IL‐33 and TSLP mediates amplified inhibition of airway inflammation and remodelling in a murine model of asthma

Wang

Zhang

et al. 2019

Respirology

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“…And diisononyl phthalate (DINP is a member of the phthalate family) was shown to suppress the polarization of Th1 and enhance the polarization of Th2 in Hwang's study 21 . You 22 detected some cytokines in bronchoalveolar lavage fluid (BALF) in asthma model, and OVA and DEHP participated a salient Th2 response which was characterized by the upregulation of Th2-type cytokines, such as IL-4, IL-5 and IL-13. However, they considered that OVA had a greater impact than DEHP in this study, which was a little inconsistent with us who considered that DEHP may act as an adjuvant.…”

Section: Discussionmentioning

confidence: 99%

Effect of di-(2-ethylhexyl) phthalate (DEHP) on allergic rhinitis

Zou

Hong

Kang

et al. 2020

Sci Rep

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Allergic rhinitis (AR) is a common chronic inflammatory disease of the upper respiratory tract. Di(2ethylhexyl) phthalate (DEHP) is a widely used plasticizer and belongs to environmental endocrine disruptors (EDCs). It can be entered the human body which is harmful to health. The relationship between DEHP and AR is still inconclusive. This study aims to investigate the effect of environmental pollutants DEHP on AR. By examining DEHP metabolites in the urine of AR patients and building an AR model. 24 BALB/c mice were used as the study subjects, and ovalbumin (OVA) and DEHP (3 mg/kg/ body) were used for intragastric administration. They were divided into control group, DEHP group, OVA group and OVA + DEHP group. Examination, behavioral scoring, inflammatory factor testing, oxidative stress testing, detection of aryl hydrocarbon receptor (AhR) and signaling pathways CYP1A1 and CYP1B1 related proteins and mRNA. The concentrations of 3 metabolites of DEHP (MEHHP, MEOHP, and MEHP) in urine of AR patients were higher. And HE-staining showed that for the control group, many chronic inflammatory cell infiltration and nasal mucosal destruction were observed in the OVA + DEHP group and were more severe than the OVA group. Allergic symptom scores were obtained from sneezing, scratching, number of scratching, and nose flow. The scores of the OVA group and the OVA + DEHP group were higher than 7 points. Serum ELISA and nasal mucosal oxidative stress tests are more serious in the OVA + DEHP group. The expression of AhR protein and its mRNA was increased in the DEHP group, OVA group and OVA + DEHP group. The OVA + DEHP group was more significant in the OVA group and DEHP group. And the mRNAs of the AhR-related signaling pathways CYP1A1 and CYP1B1 were also more prominent in the OVA + DEHP group. DEHP may aggravate its inflammatory response through the AhR pathway closely related to the environment. When combined with OVA, DEHP can further aggravate the OVA-induced nasal inflammatory response and make the nasal cavity have undergone severe changes, and many inflammatory cells have infiltrated. DEHP has shown an adjuvant effect, and the AhR-related signaling pathways CYP1A1 and CYP1B1 may be critical. Allergic rhinitis (AR) is a common upper respiratory disease. The main clinical symptoms are: paroxysmal sneezing, runny, nasal congestion and nasal itching, which may be accompanied by eye symptoms such as itching and tearing. It is plaguing 10% to 40% of the world's population, endangering human health and reducing the quality of life 1. The pathogenesis of AR is complex, and that environmental and genetic factors play a decisive role. Environmental factors have become increasingly important in recent years. Not only the atmosphere and water pollution, the study found that environmental endocrine disruptors (EDCs) are closely related to a variety of allergic diseases as a source of environmental pollution of widespread concern worldwide 2. Di(2-Ethylhexyl) Phthalate (DEHP) is a kind of EDCs, which is the most widely used and widel...

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“…But, we confirmed bronchial hyperreactivity and elevated eosinophils in BAL fluid in OVA-induced asthma model. These findings are accepted as the model of bronchial asthma in majority of OVA-induced murine asthma study [ 22 23 ]. Second, the concentration of ozone used in the present study was totally different to that of ambient ozone and of ozone used in human study.…”

Section: Discussionmentioning

confidence: 99%

Increased antioxidant activity after exposure of ozone in murine asthma model

Kim

Koo

Kim

et al. 2017

Asia Pacific Allergy

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BackgroundOzone is well known as an important component of ambient air pollutants. Ozone can aggravate respiratory symptoms in patients with bronchial asthma, but, not in healthy person. We hypothesized asthma itself may show different response to ozone compared to nonasthma.ObjectiveThis study was performed to evaluate the differences of response to ozone between normal and asthmatic mice model in terms of status of oxidant injury and antioxidant activity.MethodsThree parts per million of ozone was exposed to ovalbumin (OVA)-induced murine asthma model for 3 hours at 3, 7, 14, 21 days after completion of asthma model. Airway responsiveness to methacholine was measured after completion of asthma model. Bronchoalveolar lavage (BAL), protein extraction from lung for Western blot and immunohistochemistry of 4-hydroxy-2-nonenal (4-HNE), proliferating cell nuclear antigen (PCNA), NF-E2 related factor 2 (Nrf-2), and activity of glutathione were performed at before and each ozone exposure day.ResultsAirway hyper-responsiveness and increased eosinophils in BAL fluid were observed in asthma model. In asthma model, the expression of 4-HNE already more increased at baseline (without ozone) compared to those in sham model. This increased expression is more enhanced at 3 days after ozone exposure. The expression of PCNA was significantly increased in OVA-model compared to those in sham model. The expression of Nrf-2 was observed at baseline, and 3 and 7 days after exposure ozone in asthma model, but not in sham model. The activity of glutathione increased significantly after exposure of ozone, but not in sham model.ConclusionMurine asthma model has enhanced oxygen toxicity and antioxidant activity response to ozone.

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Thymic Stromal Lymphopoietin Neutralization Inhibits the Immune Adjuvant Effect of Di-(2-Ethylhexyl) Phthalate in Balb/c Mouse Asthma Model

Cited by 22 publications

References 49 publications

Combined blockade of IL‐25, IL‐33 and TSLP mediates amplified inhibition of airway inflammation and remodelling in a murine model of asthma

Combined blockade of IL‐25, IL‐33 and TSLP mediates amplified inhibition of airway inflammation and remodelling in a murine model of asthma

Effect of di-(2-ethylhexyl) phthalate (DEHP) on allergic rhinitis

Increased antioxidant activity after exposure of ozone in murine asthma model

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