Adenovirus expressing Fas ligand gene decreases airway hyper-responsiveness and eosinophilia in a murine model of asthma

Chuang, Ya Hui; Cl, Fu; Yc, Lo; Chiang, Bor‐Luen

doi:10.1038/sj.gt.3302325

Cited by 24 publications

(18 citation statements)

References 52 publications

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“…The whole-body plethysmography was measured with the Penh system (Penh ¼ pause Â (peak expiratory box flow/peak inspiratory box flow)) as described previously. 35,36 Briefly, mice were placed in the main chamber of a whole-body plethysmography and challenged with aerosolized normal saline, and later challenged with increasing doses of MCh (6.25-50 mg ml À1 ; Sigma, St Louis, MO, USA). Results were expressed for each concentration of MCh as a percentage of the baseline Penh value after exposure to normal saline.…”

Section: Determination Of the Airway Functionmentioning

confidence: 99%

Small interfering RNA against interleukin-5 decreases airway eosinophilia and hyper-responsiveness

Huang

Chiang

2008

Gene Ther

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Interleukin-5 (IL-5) has been suggested to be involved in the development of airway hyper-responsiveness (AHR). Both clinical and experimental investigations have shown strong correlation between the presence of eosinophils and AHR. In this study, we used small interfering RNA (siRNA) as an approach to inhibiting the expression of IL-5 and reducing AHR. siRNAs targeting IL-5 were characterized in vitro, and siRNA-expressing lentiviruses were administered intratracheally to OVA-sensitized BALB/c mice. AHR, cytokine levels, serum levels of OVA-specific antibodies and infiltration of inflammatory cells were analyzed to investigate the effects of siRNA in an OVA-induced murine model of asthma. Lentivirus-delivered siRNA targeting IL-5 efficiently moderated the characteristics of asthma, including AHR, cellular infiltration of lung tissues, eotaxin levels in the bronchoalveolar lavage fluid and IL-5 mRNA levels in lungs in the mouse model of asthma. However, there was no effect on OVA-specific IgE level. These data demonstrate that siRNA delivered by the lentiviral system is an efficacious therapeutic strategy for asthma.

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Section: Determination Of the Airway Functionmentioning

confidence: 99%

Small interfering RNA against interleukin-5 decreases airway eosinophilia and hyper-responsiveness

Huang

Chiang

2008

Gene Ther

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“…Fas ligand (FasL) is another target that mediates the apoptotic pathway in lymphocytes. Chuang et al delivered FasL intratracheally using an adenoviral vector and showed an attenuation of AHR and airway eosinophilia (due to an increase in eosinophil apoptosis), as well as a decrease in IL-5, IL-13, and eotaxin in BAL [122].…”

Section: Therapeutic Potential Of Dna Gene Therapy For Asthmamentioning

confidence: 97%

New Biological Approaches in Asthma: DNA-Based Therapy

Wang

Lee²,

Yang³

et al. 2007

CMC

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Asthma is characterized by airway inflammation, bronchial hyper-responsiveness, and reversible airway obstruction. Medications for asthma include corticosteroids, b2-adrenergic receptor agonists, chromones, methylxanthines, and leukotriene modifiers. Despite these advances in therapy, many symptoms are not well controlled. Since asthma is a chronic airway inflammation with a bias towards a type 2 T helper (Th2) cell response, some new approaches are targeted towards the Th2 inflammation pathway. These include anti-IgE therapy, anti-Th2 cytokine therapy, and therapies aiming at increasing Th1 cytokines. This article will focus on DNA-based therapy, a novel therapeutic strategy for asthma. Immunostimulatory gene therapy using CpG oligodeoxynucleotides with central deoxycytidyl-deoxyguanosine (CpG) dinucleotide, in which the cytosine nucleobase is unmethylated, can stimulate the innate immunity and augment Th1 response. With DNA gene therapy, genes can be introduced to target Th1 cytokines or other mediators in the airway in order to counteract Th2 inflammation in asthma. Also, antisense oligonucleotides can target mRNA species of interest in asthma. Through these therapies, we can expect long-lasting effects, better control of symptoms, and reducing medication in the future.

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“…11 For systemic immunization, mice were sensitized by intraperitoneal injection of 50 mg of OVA (Sigma, St Louis, MO, USA) mixed with 4 mg of alum on day 0; they were then given 25 mg of OVA mixed with 4 mg of alum on days 14, 21 and 28. On days 42, 43 and 44, mice were challenged with 100 mg/ mouse (in a total volume of 40 ml) of OVA by intranasal administration.…”

Section: Immunization and As 2 O 3 Treatmentmentioning

confidence: 99%

Arsenic trioxide alleviates airway hyperresponsiveness and eosinophilia in a murine model of asthma

et al. 2010

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Asthma is one of the most common chronic airway inflammatory diseases. The clinical hallmarks of asthma include elevated serum levels of immunoglobulin E (IgE), eosinophilic inflammation and airway hyper-responsiveness (AHR). Arsenic trioxide (As 2 O 3 ) is considered a carcinogen; however, it has also been used to treat diseases, such as syphilis, in traditional Chinese and Western medicine. Today, As 2 O 3 is used as one of the standard therapies for acute promyelocytic leukemia (APL). Previous studies have indicated that As 2 O 3 can induce apoptosis in eosinophils. However, the effect of As 2 O 3 on asthma has not been investigated. We used ovalbumin (OVA)-immunized mice as a model for asthma and treated mice with As 2 O 3 at doses of 2.5 and 5 mg/kg. The mice were then monitored for OVA-specific IgE production, airway inflammatory cell infiltration and AHR. We found that administration of As 2 O 3 in OVA-immunized mice abrogated airway eosinophil recruitment by downregulating eotaxin expression but did not alter serum IgE or IL-5 levels in bronchoalveolar lavage fluid (BALF). Furthermore, the development of AHR and cellular infiltration into the airway were reduced by treating mice with As 2 O 3 . In vitro data suggested that low concentrations of As 2 O 3 could induce only a small degree of apoptosis in primary pulmonary cells but could significantly inhibit the secretion of eotaxin by these cells. These results indicate that the administration of As 2 O 3 to OVA-immunized mice can suppress lung allergic inflammatory responses. As 2 O 3 might therefore have therapeutic potential in treating allergic airway inflammatory diseases.

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Adenovirus expressing Fas ligand gene decreases airway hyper-responsiveness and eosinophilia in a murine model of asthma

Cited by 24 publications

References 52 publications

Small interfering RNA against interleukin-5 decreases airway eosinophilia and hyper-responsiveness

Small interfering RNA against interleukin-5 decreases airway eosinophilia and hyper-responsiveness

New Biological Approaches in Asthma: DNA-Based Therapy

Arsenic trioxide alleviates airway hyperresponsiveness and eosinophilia in a murine model of asthma

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