Bronchial epithelium as a target for innovative treatments in asthma

Gras, Delphine; Chanez, Pascal; Vachier, Isabelle; Petit, Audrey; Bourdin, Arnaud

doi:10.1016/j.pharmthera.2013.07.008

Cited by 113 publications

(89 citation statements)

References 292 publications

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“…Daidzein decreased mRNA levels of the chemokine Cxcl2 induced by TNF-α Because bronchoalveolar epithelial cells are critical defense barrier against exogenous pathogens and are implicated in the initiation of inflammation in lungs by TNF-α and under various pulmonary disease conditions [24][25][26] , we utilized murine MLE-12 epithelial cells to obtain insight into the molecular mechanism by which daidzein inhibits inflammation. MLE-12 cells were transfected with the Cxcl2-luc reporter plasmid and then exposed to TNF-α (20 ng/mL) in the presence or absence of daidzein or PJ34.…”

Section: Wwwchinapharcom LI Hy Et Almentioning

confidence: 99%

Daidzein suppresses pro-inflammatory chemokine Cxcl2 transcription in TNF-α-stimulated murine lung epithelial cells via depressing PARP-1 activity

Pan

et al. 2014

Acta Pharmacol Sin

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Aim: Daidzein (4′,7-dihydroxyisoflavone) is an isoflavone exiting in many herbs that has shown anti-inflammation activity. The aim of this study was to investigate the mechanism underlying its anti-inflammatory action in murine lung epithelial cells. Methods: C57BL/6 mice were intranasally exposed to TNF-α to induce lung inflammation. The mice were injected with daidzein (400 mg/kg, ip) before TNF-α challenge, and sacrificed 12 h after TNF-α challenge, and lung tissues were collected for analyisis. In in vitro studies, murine MLE-12 epithelial cells were treated with TNF-α (20 ng/mL). The expression of pro-inflammatory chemokine Cxcl2 mRNA and NF-κB transcriptional activity were examined using real-time PCR and a dual reporter assay. Protein poly-adenosine diphosphate-ribosylation (PARylation) was detecyed using Western blotting and immunoprecipitation assays. Results: Pretreatment of the mice with daidzein markedly attenuated TNF-α-induced lung inflammation, and inhibited Cxcl2 expression in lung tissues. Furthermore, daidzein (10 μmol/L) prevented TNF-α-induced increases in Cxcl2 expression and activity and NF-κB transcriptional activity, and markedly inhibited TNF-α-induced protein PARylation in MLE-12 cells in vitro. In MLE-12 cells co-transfected with the PARP-1 expression plasmid and NF-κB-luc (or Cxcl2-luc) reporter plasmid, TNF-α markedly increased NF-κB (or Cxcl2) activation, which were significantly attenuated in the presence of daidzein (or the protein PARylation inhibitor PJ 34). PARP-1 activity assay showed that daidzein (10 μmol/L) reduced the activity of PARP-1 by ~75%. Conclusion: The anti-inflammatory action of daidzein in murine lung epithelial cells seems to be mediated via a direct interaction with PARP-1, which inhibits RelA/p65 protein PARylation required for the transcriptional modulation of pro-inflammatory chemokines such as Cxcl2.

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Section: Wwwchinapharcom LI Hy Et Almentioning

confidence: 99%

Daidzein suppresses pro-inflammatory chemokine Cxcl2 transcription in TNF-α-stimulated murine lung epithelial cells via depressing PARP-1 activity

Pan

et al. 2014

Acta Pharmacol Sin

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“…Therapeutic targets in asthmatic adults were discussed in a previous review [72]. Numerous biological therapies have been developed targeting the different biological steps involved in this inflammatory disease.…”

Section: Innate Immune Responsesmentioning

confidence: 99%

Bronchial epithelium in children: a key player in asthma

et al. 2016

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Bronchial epithelium is a key element of the respiratory airways. It constitutes the interface between the environment and the host. It is a physical barrier with many chemical and immunological properties. The bronchial epithelium is abnormal in asthma, even in children. It represents a key component promoting airway inflammation and remodelling that can lead to chronic symptoms. In this review, we present an overview of bronchial epithelium and how to study it, with a specific focus on children. We report physical, chemical and immunological properties from ex vivo and in vitro studies. The responses to various deleterious agents, such as viruses or allergens, may lead to persistent abnormalities orchestrated by bronchial epithelial cells. As epithelium dysfunctions occur early in asthma, reprogramming the epithelium may represent an ambitious goal to induce asthma remission in children. @ERSpublications Bronchial epithelium is a morphological and functional dysregulated gatekeeper in asthmatic children http://ow.ly/Y4MaM

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“…Lipoxin A4, a mediator derived from the arachidonic metabolism, has been shown to promote the resolution of inflammation linked to innate immunity by inhibiting the in vitro release of IL-13 by type-2 innate lymphoid cells and promoting the apoptosis of eosinophils induced by natural killer cells. Because of the potential defect of lipoxin and other pro-resolution mediators released in severe asthma, hyperactivation of innate immunity may participate in the perpetuation of airway inflammation in these patients, despite current pharmacological treatments [3,7,8].…”

Section: @Erspublicationsmentioning

confidence: 99%

“…New interventions are currently under development for severe asthma [7,[9][10][11]. The anti-IL-5 strategy is the most advanced.…”

Section: @Erspublicationsmentioning

confidence: 99%

Asthma: still a promising future?

Chanez

Humbert

2014

Eur Respir Rev

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@ERSpublicationsThe pathobiology of asthma is better understood but most of the treatments are still symptomdriven controllers http://ow.ly/CUxjyTo date, asthma remains one of the most frequent chronic diseases in children and adults worldwide [1,2]. Despite our increased knowledge of the mechanisms and treatments of asthma, we need to better understand the natural history of this lifelong disease. In mild asthma, compliance and adherence to existing and efficient therapies are the main problem whereas in severe asthma, innovative treatments are the new challenges to better control the disease [3][4][5]. A new series on asthma is, therefore, very welcome in the European Respiratory Review in order to focus on specific areas discussed in recent findings. These series articles, written by expert opinion leaders, can be used to stimulate new ideas as well as provide new forms of management and treatment [6]. The articles deal with hot topics requiring balanced expertise and opinion. The experts will discuss new views on those important questions for researchers and physicians.The continuing increase in asthma prevalence (more than 400 million cases by 2020) points to a potential role of risk factors. Genetic background is obvious but multiple genes are involved and have been shown to be influenced by environmental factors (epigenetics), even during the gestation period. Lifestyle and environmental exposures are the most commonly studied risk factors. Their role in the inception of asthma is still a matter of debate and despite much research between allergy and asthma the causality between the two has yet to be demonstrated. The hygiene hypothesis is an elegant way to bring together the development of a switch of the immune system and contact with a specific microbial environment. A specific link with nurture is suspected in children with some specific genetic polymorphisms, but again allergy and asthma are not completely discriminated in most studies. The geolocalisation of the subjects (using personal GPS) and the precise environmental exposure to pollutants, allergens and microbes may help to define a more personalised risk to developing the disease [1].The characteristic mechanisms of asthma include bronchial hyperreactivity, airway inflammation and structural changes of the airways. These different pathways may explain many of the clinical phenotypes, symptoms and exacerbations, and perhaps natural history, of the disease. Eosinophils are key players as the major granulocytes that are recruited, activated and survive within the airway wall, and also migrate to the epithelium lumen [1]. Asthmatic inflammation is associated with an eosinophilic T-helper (Th)2-driven mechanism based on the release of cytokines, such as interleukin (IL)-5, IL-4 and IL-13. This wellestablished inflammation model is based on various allergic responses requiring an adaptive immune pathway. More recently, it was found that bronchial epithelial cells can communicate with immune cells, such as dendritic cells and innate lymphocytes, thou...

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Bronchial epithelium as a target for innovative treatments in asthma

Cited by 113 publications

References 292 publications

Daidzein suppresses pro-inflammatory chemokine Cxcl2 transcription in TNF-α-stimulated murine lung epithelial cells via depressing PARP-1 activity

Daidzein suppresses pro-inflammatory chemokine Cxcl2 transcription in TNF-α-stimulated murine lung epithelial cells via depressing PARP-1 activity

Bronchial epithelium in children: a key player in asthma

Asthma: still a promising future?

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