scholarly journals Tomatidine Attenuates Airway Hyperresponsiveness and Inflammation by Suppressing Th2 Cytokines in a Mouse Model of Asthma

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Chieh-Ying Kuo ◽  
Wen-Chung Huang ◽  
Chian-Jiun Liou ◽  
Li-Chen Chen ◽  
Jiann-Jong Shen ◽  
...  

Tomatidine is isolated from the fruits of tomato plants and found to have anti-inflammatory effects in macrophages. In the present study, we investigated whether tomatidine suppresses airway hyperresponsiveness (AHR) and eosinophil infiltration in asthmatic mice. BALB/c mice were sensitized with ovalbumin and treated with tomatidine by intraperitoneal injection. Airway resistance was measured by intubation analysis as an indication of airway responsiveness, and histological studies were performed to evaluate eosinophil infiltration in lung tissue. Tomatidine reduced AHR and decreased eosinophil infiltration in the lungs of asthmatic mice. Tomatidine suppressed Th2 cytokine production in bronchoalveolar lavage fluid. Tomatidine also blocked the expression of inflammatory and Th2 cytokine genes in lung tissue. In vitro, tomatidine inhibited proinflammatory cytokines and CCL11 production in inflammatory BEAS-2B bronchial epithelial cells. These results indicate that tomatidine contributes to the amelioration of AHR and eosinophil infiltration by blocking the inflammatory response and Th2 cell activity in asthmatic mice.

Antioxidants ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 295 ◽  
Author(s):  
Chian-Jiun Liou ◽  
Ya-Ling Chen ◽  
Ming-Chin Yu ◽  
Kuo-Wei Yeh ◽  
Szu-Chuan Shen ◽  
...  

Sesamol, isolated from sesame seeds (Sesamum indicum), was previously shown to have antioxidative, anti-inflammatory, and anti-tumor effects. Sesamol also inhibited lipopolysaccharide (LPS)-induced pulmonary inflammatory response in rats. However, it remains unclear how sesamol regulates airway inflammation and oxidative stress in asthmatic mice. This study aimed to investigate the efficacy of sesamol on oxidative stress and airway inflammation in asthmatic mice and tracheal epithelial cells. BALB/c mice were sensitized with ovalbumin, and received oral sesamol on days 14 to 27. Furthermore, BEAS-2B human bronchial epithelial cells were treated with sesamol to investigate inflammatory cytokine levels and oxidative responses in vitro. Our results demonstrated that oral sesamol administration significantly suppressed eosinophil infiltration in the lung, airway hyperresponsiveness, and T helper 2 cell-associated (Th2) cytokine expressions in bronchoalveolar lavage fluid and the lungs. Sesamol also significantly increased glutathione expression and reduced malondialdehyde levels in the lungs of asthmatic mice. We also found that sesamol significantly reduced proinflammatory cytokine levels and eotaxin in inflammatory BEAS-2B cells. Moreover, sesamol alleviated reactive oxygen species formation, and suppressed intercellular cell adhesion molecule-1 (ICAM-1) expression, which reduced monocyte cell adherence. We demonstrated that sesamol showed potential as a therapeutic agent for improving asthma.


2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Dong-Seon Kim ◽  
Seung-Hyung Kim ◽  
Bok-Kyu Kim ◽  
Min Cheol Yang ◽  
Jin Yeul Ma

This study was conducted to determine if oral administration of the novel herbal medicine, MA, and itsLactobacillus acidophilusfermented product, MA128, have therapeutic properties for the treatment of asthma. Asthma was induced in BALB/c mice by systemic sensitization to ovalbumin (OVA) followed by intratracheal, intraperitoneal, and aerosol allergen challenges. MA and MA128 were orally administered 6 times a week for 4 weeks. At 1 day after the last ovalbumin exposure, airway hyperresponsiveness was assessed and samples of bronchoalveolar lavage fluid, lung cells, and serum were collected for further analysis. We investigated the effect of MA and MA128 on airway hyperresponsiveness, pulmonary eosinophilic infiltration, various immune cell phenotypes, Th2 cytokine production, OVA-specific IgE production, and Th1/Th2 cytokine production in this mouse model of asthma. In BALB/c mice, we found that MA and MA128 treatment suppressed eosinophil infiltration into airways and blood, allergic airway inflammation and AHR by suppressing the production of IL-5, IL-13, IL-17, Eotaxin, and OVA-specific IgE, by upregulating the production of OVA-specific Th1 cytokine (IFN-γ), and by downregulating OVA-specific Th2 cytokine (IL-4) in the culture supernatant of spleen cells. The effectiveness of MA was increased by fermentation withLactobacillus acidophilus.


2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Wen-Chung Huang ◽  
Chian-Jiun Liou

A previous study found that eosinophil infiltration and Th2 cell recruitment are important causes of chronic lung inflammation in asthma. The plant flavonoid acacetin is known to have an anti-inflammatory effectin vitro. This study aims to investigate the anti-inflammatory effect of orally administered acacetin in ovalbumin- (OVA-) sensitized asthmatic mice and its underlying molecular mechanism. BALB/c mice were sensitized by intraperitoneal OVA injection. OVA-sensitized mice were fed acacetin from days 21 to 27. Acacetin treatment attenuated airway hyperresponsiveness and reduced eosinophil infiltration and goblet cell hyperplasia in lung tissue. Additionally, eotaxin-1- and Th2-associated cytokines were inhibited in bronchoalveolar lavage fluid and suppressed the level of OVA-IgE in serum. Human bronchial epithelial (BEAS-2B) cells were used to examine the effect of acacetin on proinflammatory cytokines, chemokines, and cell adhesion molecule productionin vitro. At the molecular level, acacetin significantly reduced IL-6, IL-8, intercellular adhesion molecule-1, and eotaxin-1 in activated BEAS-2B cells. Acacetin also significantly suppressed the ability of eosinophils to adhere to inflammatory BEAS-2B cells. These results suggest that dietary acacetin may improve asthma symptoms in OVA-sensitized mice.


2019 ◽  
Vol 47 (07) ◽  
pp. 1507-1522 ◽  
Author(s):  
Nai-Chun Ting ◽  
Wen-Chung Huang ◽  
Li-Chen Chen ◽  
Sien-Hung Yang ◽  
Ming-Ling Kuo

In Chinese medicine, Descurainia sophia is used to treat cough by removing the phlegm in asthma and inflammatory airway disease, but the mechanism is not clear. In this study, we evaluated whether D. sophia water extract (DSWE) can alleviate airway inflammation and airway hyperresponsiveness (AHR) in the lungs of a murine asthma model. Female BALB/c mice were divided into five groups: normal controls, ovalbumin (OVA)-sensitized asthmatic mice, and OVA-sensitized mice treated with DSWE (2, 4, 8 g/day) by intraperitoneal injection. After sacrificing the mice, serum was collected to detect OVA-specific antibodies by ELISA, as well as bronchoalveolar lavage fluid (BALF) to detect cytokine levels. We also detected gene expression and histopathologically evaluated the lungs of asthmatic mice. DSWE reduced AHR, goblet cell hyperplasia, eosinophil infiltration, and collagen aggregation in the lungs of asthmatic mice. DSWE also suppressed the gene expression of Th2-associated cytokines and chemokines in lung tissue and inhibited serum OVA-IgE and Th2-associated cytokine levels in the BALF of OVA-sensitized mice. Our findings suggest that DSWE is a powerful immunomodulator for ameliorated allergic reactions by suppressing Th2 cytokine expression in asthmatic mice.


2001 ◽  
Vol 281 (2) ◽  
pp. L394-L402 ◽  
Author(s):  
K. Takeda ◽  
A. Haczku ◽  
J. J. Lee ◽  
C. G. Irvin ◽  
E. W. Gelfand

Different strains of mice exhibit different degrees of airway hyperresponsiveness after sensitization to and airway challenge with ovalbumin. Antibody responses in BALB/c mice far exceeded those in C57BL/6 mice; in contrast, although responsiveness to methacholine was much higher in the BALB/c mice, the number of eosinophils in the bronchoalveolar lavage fluid was higher in C57BL/6 animals. Sensitized and challenged BALB/c mice developed increases in lung resistance and decreases in dynamic compliance after methacholine or 5-hydroxytryptamine inhalation. C57BL/6 mice only exhibited significant levels of responsiveness when dynamic compliance was monitored in response to inhaled 5-hydroxytryptamine. Eosinophils accumulated in the peribronchial and peripheral lung tissue in BALB/c mice but were distributed diffusely in the peripheral lung tissue of C57BL/6 mice. Thus, in addition to differences in antibody responses and cholinergic agonist reactivity, differences in the responses of large and small airways may reflect the selective distribution of eosinophils in lung tissue.


2020 ◽  
Vol 66 (7) ◽  
pp. 435-445
Author(s):  
Yuting Fang ◽  
Xuemei Zhang ◽  
Chang Lu ◽  
Yibing Yin ◽  
Xuexue Hu ◽  
...  

Pneumolysin (Ply) is a major virulence factor of Streptococcus pneumoniae. Ply-induced interferon-β (IFN-β) expression in host macrophages has been shown to be due to the accumulation of mitochondrial deoxyribonucleic acid (mtDNA) in the cytoplasm during S. pneumoniae infection. Our findings extend this work to show human bronchial epithelial cells that reside at the interface of inflammatory injury, BEAS-2B, adapt to local cues by altering mitochondrial states and releasing excess mtDNA. The results in this research showed that purified Ply induced the expression of IFN-β in human epithelial cells, which was accompanied by mitochondrial damage both in vivo and in vitro. The observations also were supported by the increased mtDNA concentrations in the bronchial lavage fluid of mice infected with S. pneumoniae. In summary, our study demonstrated that Ply triggered the production of IFN-β in epithelial cells, and this response was mediated by mtDNA released from Ply-damaged mitochondria. It displayed an impressive modulation of IFN-β response to S. pneumoniae in epithelial cells.


2013 ◽  
Vol 2013 ◽  
pp. 1-9
Author(s):  
Chih-Che Lin ◽  
Shulhn-Der Wang ◽  
Li-Jen Lin ◽  
Hong-Jye Hong ◽  
Chin-Jen Wu ◽  
...  

Urine therapy has been commonly practiced in ancient civilizations including those of India, China, and Greece. The traditional Chinese medicine KWLL, the precipitation of human urine, has been used in China to alleviate the symptoms of asthma for thousands of years. However, the mechanism of action by which KWLL exerts its immunotherapy is unclear. This study attempted to elucidate the pharmacology of KWLL in mice that had been challenged recurrently byDermatophagoides pteronyssinus(Der p). BALB/c mice were orally administered KWLL (1 g/kg) before an intratracheal (i.t.) challenge of Der p. Allergic airway inflammation and remodeling were provoked by repetitive Der p (50 μg/mice) challenges six times at 1 wk intervals. Airway hypersensitivity, histological lung characteristics, and the expression profiles of cytokines and various genes were assessed. KWLL reduced Der p-induced airway hyperresponsiveness and inhibited eosinophil infiltration by downregulating the protein expression of IL-5 in bronchoalveolar lavage fluid (BALF). It also inhibited neutrophil recruitment by downregulating IL-17A in BALF. KWLL effectively diminished inflammatory cells, goblet cell hyperplasia, and mRNA expression of IL-6 and IL-17A in the lung. The reduction by KWLL of airway inflammatory and hyperresponsiveness in allergic asthmatic mice was mediated via immunomodulation of IL-5, IL-6, and IL-17A.


1991 ◽  
Vol 260 (6) ◽  
pp. L530-L538 ◽  
Author(s):  
M. Soloperto ◽  
V. L. Mattoso ◽  
A. Fasoli ◽  
S. Mattoli

We have examined the in vitro interaction between bronchial epithelial cells and eosinophils derived from five asthmatics by determining the effect of epithelial cell-conditioned medium on the survival and activation of peripheral blood eosinophils. The supernatants of epithelial cells from six normal donors were used as control. The asthmatic epithelial cell-conditioned medium significantly increased the survival of eosinophils cultured for 3 (P less than 0.025) and 6 (P less than 0.05) days. The incubation of eosinophils with the supernatants of asthmatic epithelial cells for 1 h also increased the generation of superoxide anion and the release of leukotriene C4, triggered by phorbol myristate acetate and calcium ionophore, by more than twofold. The preincubation of asthmatic epithelial cell-conditioned media with saturating concentrations of a mono-specific antiserum against granulocyte-macrophage colony-stimulating factor (GM-CSF) completely abolished their activity, whereas the addition of recombinant human GM-CSF restored it. The supernatants of asthmatic epithelial cells contained 0.88 +/- 0.09 (SD) ng/5 X 10(5) cells immunoreactive GM-CSF, and this amount was significantly greater than that measured in the supernatants of normal epithelial cells (0.21 +/- 0.105, P less than 0.025). Bronchial epithelial cells from asthmatics also expressed increased levels of GM-CSF mRNA when compared with normal epithelial cells. Thus both the synthesis and release of GM-CSF by bronchial epithelial cells are upregulated in asthma, and this may contribute to the persistence of eosinophil infiltration and activation in asthmatic airways.


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