Suppression of heme oxygenase-1 activity reduces airway hyperresponsiveness and inflammation in a mouse model of asthma

Kuribayashi, Kozo; Iida, Shinichiro; Nakajima, Yasuhiro; Funaguchi, Norihiko; Tabata, Chiharu; Fukuoka, Kazuya; Fujimori, Yoshihiro; Ihaku, Daizo; Nakano, Takashi

doi:10.3109/02770903.2015.1008138

Cited by 14 publications

(10 citation statements)

References 29 publications

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“…Air flow and respiratory rate can be detected to evaluate the pathological characteristics and respiratory system of asthma patients [48]. Previous studies found that oxidative stress and inflammatory mediators can stimulate excessive AHR and cause deterioration of lung function [15,49]. Airway narrowing and dyspnea are the most common symptoms, and the result increases airway resistance and excessive expansion in the lungs of asthmatic patients [50].…”

Section: Discussionmentioning

confidence: 99%

“…Licochalcone A is a chalcone isolated from Glycyrrhiza uralensis Fisch [12]. Licochalcone A has multiple biological functions in cellular and animal models, and it has been demonstrated to reduce the inflammatory response in lipopolysaccharide (LPS)-stimulated macrophages and induce apoptosis and autophagy in tumor cells [13,14,15,16]. Licochalcone A could also decrease ROS, promoting neuroprotective effects [17].…”

Section: Introductionmentioning

confidence: 99%

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Protective Effects of Licochalcone A Improve Airway Hyper-Responsiveness and Oxidative Stress in a Mouse Model of Asthma

Huang

Liu

Shen

et al. 2019

Cells

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Licochalcone A was isolated from Glycyrrhiza uralensis and previously reported to have antitumor and anti-inflammatory effects. Licochalcone A has also been found to inhibit the levels of Th2-associated cytokines in the bronchoalveolar lavage fluid (BALF) of asthmatic mice. However, the molecular mechanism underlying airway inflammation and how licochalcone A regulates oxidative stress in asthmatic mice are elusive. In this study, we investigated whether licochalcone A could attenuate inflammatory and oxidative responses in tracheal epithelial cells, and whether it could ameliorate oxidative stress and airway inflammation in asthmatic mice. Inflammatory human tracheal epithelial (BEAS-2B) cells were treated with licochalcone A to evaluate oxidative responses and inflammatory cytokine levels. In addition, BALB/c mice were sensitized with ovalbumin (OVA) and injected intraperitoneally with licochalcone A (5 or 10 mg/kg). Licochalcone A significantly inhibited reactive oxygen species, eotaxin, and proinflammatory cytokines in BEAS-2B cells. Licochalcone A also decreased intercellular adhesion molecule 1 levels in inflammatory BEAS-2B cells, blocking monocyte cell adherence. We also found that licochalcone A significantly decreased oxidative responses, reduced malondialdehyde levels, and increased glutathione levels in the lungs of OVA-sensitized mice. Furthermore, licochalcone A decreased airway hyper-responsiveness, eosinophil infiltration, and Th2 cytokine production in the BALF. These findings suggest that licochalcone A alleviates oxidative stress, inflammation, and pathological changes by inhibiting Th2-associated cytokines in asthmatic mice and human tracheal epithelial cells. Thus, licochalcone A demonstrated therapeutic potential for improving asthma.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Protective Effects of Licochalcone A Improve Airway Hyper-Responsiveness and Oxidative Stress in a Mouse Model of Asthma

Huang

Liu

Shen

et al. 2019

Cells

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“…Yu and colleagues suggested that OVA-sensitized guinea pigs showed significantly enhanced expression of the HO-1 gene, which was significantly suppressed after dexamethasone treatment27. Kuribayashi and colleagues also suggested that suppression of HO-1 activity by zinc protoporphyrin (a competitive HO-1 inhibitor) resulted in inhibition of airway hyperresponsiveness and pulmonary eosinophilia28. Therefore, suppression of HO-1 could be a promising potential target for antiallergic treatment262930.…”

Section: Discussionmentioning

confidence: 99%

Hormetic Effect of Chronic Hypergravity in a Mouse Model of Allergic Asthma and Rhinitis

Jang

Jung

Kim

2016

Sci Rep

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We aimed to evaluate the effect of chronic hypergravity in a mouse model of allergic asthma and rhinitis. Forty BALB/c mice were divided as: group A (n = 10, control) sensitized and challenged with saline, group B (n = 10, asthma) challenged by intraperitoneal and intranasal ovalbumin (OVA) to induce allergic asthma and rhinitis, and groups C (n = 10, asthma/rotatory control) and D (n = 10, asthma/hypergravity) exposed to 4 weeks of rotation with normogravity (1G) or hypergravity (5G) during induction of asthma/rhinitis. Group D showed significantly decreased eosinophils, neutrophils, and lymphocytes in their BAL fluid compared with groups B and C (p < 0.05). In real-time polymerase chain reaction using lung homogenate, the expression of IL-1β was significantly upregulated (p < 0.001) and IL-4 and IL-10 significantly downregulated (p < 0.05) in group D. Infiltration of inflammatory cells into lung parenchyma and turbinate, and the thickness of respiratory epithelium was significantly reduced in group D (p < 0.05). The expression of Bcl-2 and heme oxygenase-1 were significantly downregulated, Bax and extracellular dismutase significantly upregulated in Group D. Therefore, chronic hypergravity could have a hormetic effect for allergic asthma and rhinitis via regulation of genes involved in antioxidative and proapoptotic pathways. It is possible that we could use hypergravity machinery for treating allergic respiratory disorders.

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“…These antioxidant defense effects of Nrf2 signal transduction by coptisine seem to play an important role in regulating cell proliferation and apoptosis. Zinc protoporphyrin IX (ZnPP), on the other hand, is a type of metalloporphyrins found in red blood cells when heme production is suppressed (Cheng et al 2012;Kuribayashi et al 2015). ZnPP competitively suppresses the activity of heme oxygenase-1 (HO-1), one of the major genes regulated by Nrf2, due to its similarity to heme in the porphyrin loop structure, and reduce bilirubin production rates.…”

Section: Introductionmentioning

confidence: 99%

Activation of the Nrf2/HO-1 signaling pathway contributes to the protective effects of coptisine against oxidative stress-induced DNA damage and apoptosis in HaCaT keratinocytes

Choi

2019

gpb

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In this study, the protective effect of coptisine on the oxidative damage-mediated apoptosis was evaluated in cultured human HaCaT keratinocytes. The results demonstrate that preincubation of cells with coptisine prior to H 2 O 2 stimulation resulted in significant inhibition of cytotoxicity and DNA damage associated with the inhibition of reactive oxygen species (ROS) accumulation. Coptisine also restored H 2 O 2-induced mitochondrial dysfunction and decrease of ATP production, and prevented apoptosis by inhibiting Bax/Bcl-2 ratio, caspase-3 activity, and poly(ADP-ribose) polymerase degradation. Interestingly, the expressions of nuclear factor-erythroid-2-related factor 2 (Nrf2) and its active form, phosphorylated Nrf2, were strikingly promoted by coptisine in the presence of H 2 O 2 , which was associated with a marked increase in the expression of heme oxygenase-1 (HO-1). However, coptisine-induced HO-1 expression was completely abrogated by Nrf2-specific small interfering RNA (Nrf2-siRNA), which suggests that the increased expression of HO-1 by coptisine is Nrf2-dependent. In addition, Nrf2-siRNA transfection significantly eliminated the protective effect of coptisine on H 2 O 2-induced cytotoxicity, and this effect was similar to that by zinc protoporphyrin IX (ZnPP), an HO-1 specific inhibitor. Furthermore, the protective effects of coptisine against H 2 O 2-induced cytotoxicity were abolished by ZnPP, indicating that coptisine protects keratinocytes against oxidative stress-induced injury through activation of the Nrf2/HO-1 signaling pathway.

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Suppression of heme oxygenase-1 activity reduces airway hyperresponsiveness and inflammation in a mouse model of asthma

Abstract: Expression of HO-1 is induced in lung tissue during attacks of allergic bronchial asthma, and its activity likely amplifies and prolongs allergic airway inflammation.

Cited by 14 publications

References 29 publications

Protective Effects of Licochalcone A Improve Airway Hyper-Responsiveness and Oxidative Stress in a Mouse Model of Asthma

Protective Effects of Licochalcone A Improve Airway Hyper-Responsiveness and Oxidative Stress in a Mouse Model of Asthma

Hormetic Effect of Chronic Hypergravity in a Mouse Model of Allergic Asthma and Rhinitis

Activation of the Nrf2/HO-1 signaling pathway contributes to the protective effects of coptisine against oxidative stress-induced DNA damage and apoptosis in HaCaT keratinocytes

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