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Asthma challenge model

Melissa Dullaers, Martijn J Schuijs, Monique Willart, Kaat Fierens, Justine Van Moorleghem, Hamida Hammad, Bart N Lambrecht
BACKGROUND: Allergic asthma is a CD4 Th2-lymphocyte driven disease characterized by airway hyper-responsiveness and eosinophilia. B cells can present antigens to CD4 T cells and produce IgE immunoglobulins which arms effector cells, however mouse models are inconclusive whether B cells are necessary for asthma development. OBJECTIVES: To address the role of B cells in a house dust mite (HDM) driven Th2-high asthma mouse model. METHODS: WT and B cell deficient muMT Mice were sensitized and challenged via the airways with HDM extracts...
October 13, 2016: Journal of Allergy and Clinical Immunology
H Vroman, I M Bergen, B W S Li, J A C van Hulst, M Lukkes, D van Uden, R W Hendriks, M Kool
BACKGROUND: Chronic exposure to environmental triggers, such as house dust mite (HDM), drives T helper 2 (Th2) cell-mediated asthma. Recent evidence has shown that B-T cell interaction, and in particular germinal center reactions and follicular T helper (Tfh) cells are required for the development of eosinophilic airway inflammation in HDM-driven models containing a sensitization and challenge phase. Whether B-T cell interactions are essential for pulmonary eosinophilic inflammation following chronic allergen provocation remains unknown...
October 15, 2016: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
Woo-Young Jeon, In-Sik Shin, Hyeun-Kyoo Shin, Seong Eun Jin, Mee-Young Lee
Gumiganghwal-tang is a traditional herbal prescription that is used widely for the treatment of the common cold and inflammatory diseases in Korea and other Asian countries. In this study, we investigated the protective effects of a Gumiganghwal-tang aqueous extract (GGTA) against airway inflammation and pulmonary fibrosis using a mouse model of chronic asthma. Chronic asthma was modeled in BALB/c mice via sensitization/challenge with an intraperitoneal injection of 1% ovalbumin (OVA) and inhalation of nebulized 1% OVA for 4 weeks...
2016: PloS One
Thomas Westergren, Sveinung Berntsen, Karin C Lødrup Carlsen, Petter Mowinckel, Geir Håland, Liv Fegran, Kai-Håkon Carlsen
BACKGROUND: Children with asthma may be less physically active than their healthy peers. We aimed to investigate if perceived exercise limitation (EL) was associated with lung function or bronchial hyperresponsiveness (BHR), socio-economic factors, prenatal smoking, overweight, allergic disease, asthma severity or physical activity (PA). METHODS: The 302 children with asthma from the 10-year examination of the Environment and Childhood Asthma birth cohort study underwent a clinical examination including perceived EL (structured interview of child and parent(s)), measure of overweight (body mass index by sex and age passing through 25kg/m(2) or above at18 years), exercise-induced bronchoconstriction (forced expiratory volume in one second (FEV1 ) pre- and post-exercise), methacholine bronchial challenge (severe BHR; provocative dose causing ≥20% decrease in FEV1≤1μmol) and asthma severity score (dose of controller medication and exacerbations last 12 months)...
October 13, 2016: Pediatric Allergy and Immunology
Yen Leong Chua, Ka Hang Liong, Chiung-Hui Huang, Hok Sum Wong, Qian Zhou, Say Siong Ler, Yafang Tang, Chin Pei Low, Hui Yu Koh, I-Chun Kuo, Yongliang Zhang, W S Fred Wong, Hong Yong Peh, Hwee Ying Lim, Moyar Qing Ge, Angela Haczku, Veronique Angeli, Paul A MacAry, Kaw Yan Chua, David M Kemeny
Previous studies have highlighted the importance of lung-draining lymph nodes in the respiratory allergic immune response, whereas the lung parenchymal immune system has been largely neglected. We describe a new in vivo model of respiratory sensitization to Blomia tropicalis, the principal asthma allergen in the tropics, in which the immune response is focused on the lung parenchyma by transfer of Th2 cells from a novel TCR transgenic mouse, specific for the major B. tropicalis allergen Blo t 5, that targets the lung rather than the draining lymph nodes...
October 12, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Zhongjuan Liu, Huaxia Chen, Xiaolan Chen, Jinming Gao, Zijian Guo
Chemokine C-X-C motif receptor 3 (CXCR3) is a chemokine receptor that is mainly expressed by activated T lymphocytes. T cells play important roles in allergic pulmonary inflammation, which is a hallmark of asthma and elicits the localized accumulation of activated T cells in the lung. In China, a marked increase in the incidence rate of chronic allergic pulmonary inflammation has made it a major public health threat. In the present study, we investigated the role of CXCR3 and its ligands in airway inflammation induced by house dust mite protein (HDMP) in a CXCR3 knockout (CXCR3KO) asthma mouse model...
2016: PloS One
Diamanda Rigas, Gavin Lewis, Jennifer L Aron, Bowen Wang, Homayon Banie, Ishwarya Sankaranarayanan, Lauriane Galle-Treger, Hadi Maazi, Richard Lo, Gordon J Freeman, Arlene H Sharpe, Pejman Soroosh, Omid Akbari
BACKGROUND: Atopic diseases including asthma exacerbate type 2 immune responses and involve a number of immune cell types, including regulatory T cells (Tregs) and the emerging group 2 innate lymphoid cells (ILC2s). While ILC2s are potent producers of type 2 cytokines, the regulation of ILC2 activation and function is not well understood. OBJECTIVE: In the present study, we evaluate for the first time how Tregs interact with pulmonary ILC2s and control their function...
October 4, 2016: Journal of Allergy and Clinical Immunology
Xia Yang, Jian-Ning Lv, Hui Li, Bo Jiao, Qiu-Hong Zhang, Yong Zhang, Jie Zhang, Yan-Qin Liu, Ming Zhang, Hu Shan, Jin-Zhao Zhang, Run-Miao Wu, Ya-Li Li
OBJECTIVES: Asthma is a chronic inflammatory, heterogeneous airway disease affecting millions of people around the world. Curcumin has been found to have anti-inflammatory and antifibrosis effects. Researchers reported that curcumin regulated Wnt/b-catenin signaling in lots of cells. However, whether curcumin regulates the levels of Wnt/ b-Catenin signaling in lung tissues and DCs (dendritic cells) remains unclear. In this study, we assessed the effects of curcumin on DCs and asthma. METHODS: C57BL/6 mice immunized with OVA (ovalbumin) were challenged thrice with an aerosol of OVA every second day for 8 days...
August 15, 2016: Journal of Asthma: Official Journal of the Association for the Care of Asthma
Fei Xu, Xiuhua Kang, Liang Chen, Chuanhui Chen, Gen Hu, Wei Bai, Wei Zhang
Asthma is a common chronic inflammatory disease in the airways with wide prevalence, and it is thought to be caused by the combinational factors in environment and genetics. A large body of studies has suggested that cell immunity played a vital role in regulating the airway hyperreactivity (AHR) and inflammation. Therefore, we here developed a mouse model of asthma by microinjecting the pronucleus with a vector spontaneously coding human IL10 and TGFB1 gene to explore the possible interaction between these two potent molecules during asthma progression...
October 1, 2016: Transgenic Research
Kyung-Hwa Jung, Hyunjung Baek, Dasom Shin, Gihyun Lee, Sangwon Park, Sujin Lee, Dabin Choi, Woojin Kim, Hyunsu Bae
Asthma is a common chronic disease characterized by bronchial inflammation, reversible airway obstruction, and airway hyperresponsiveness (AHR). Current therapeutic options for the management of asthma include inhaled corticosteroids and β2 agonists, which elicit harmful side effects. In the present study, we examined the capacity of phospholipase A2 (PLA2), one of the major components of bee venom (BV), to reduce airway inflammation and improve lung function in an experimental model of asthma. Allergic asthma was induced in female BALB/c mice by intraperitoneal administration of ovalbumin (OVA) on days 0 and 14, followed by intratracheal challenge with 1% OVA six times between days 22 and 30...
2016: Toxins
Jiaqi Liu, Ying Wei, Qingli Luo, Fei Xu, Zhengxiao Zhao, Hongying Zhang, Linwei Lu, Jing Sun, Feng Liu, Xin Du, Mihui Li, Kai Wei, Jingcheng Dong
Baicalin, extracted and purified from the Chinese medicinal plant, Scutellaria baicalensis Georgi (Huang qin in Chinese), exhibits potent anti-inflammatory activity against asthma. However, it remains unknown whether baicalin inhibits the activity of CC chemokine receptor 7 (CCR7) and its ligands, which are crucial for the initiation of airway inflammation. In the present study, we investigated the effects of baicalin on CCR7 and its ligands, CCL19 and CCL21, as well as on the nuclear factor-κB (NF-κB) pathway in a mouse model of asthma...
September 21, 2016: International Journal of Molecular Medicine
Yuan Lu, Jian-Ya Xu, Xiao-Hua Zhang, Xia Zhao
ETHNOPHARMACOLOGICAL RELEVANCE: In recent years, asthma has increased dramatically in prevalence with a considerable economic burden all over the world. Long-term remission should be regarded as the promising and meaningful therapeutic goal in asthma management. However, the precise definition criteria and rational therapies for asthma remission have not been well-established. In academia, there is a consensus that even in those who develop asymptomatic remission of asthma, persistent airway inflammation is ubiquitous...
November 4, 2016: Journal of Ethnopharmacology
Na Wang, Di Yan, Yi Liu, Yao Liu, Xianmin Gu, Jian Sun, Fei Long, Shujuan Jiang
BACKGROUND: Asthma is a worldwide health burden with an alarming prevalence. For years, asthma-associated airway injury remains elusive. Transforming growth factor β1 (TGF-β1) is a pleiotropic cytokine that has been shown to be involved in the synthesis of the matrix molecules associated with airway remodeling. Human antigen R (HuR), the member of the Hu RNA-binding protein family, can bind to a subset of short-lived mRNAs in their 3' untranslated regions (UTR). However, the functional roles and relevant signaling pathways of HuR in airway remodeling have not been well illustrated...
2016: Respiratory Research
S-S Rao, Q Mu, Y Zeng, P-C Cai, F Liu, J Yang, Y Xia, Q Zhang, L-J Song, L-L Zhou, F-Z Li, Y-X Lin, J Fang, P A Greer, H-Z Shi, W-L Ma, Y Su, H Ye
BACKGROUND: Allergic asthma is characterized by inflammation and airway remodelling. Airway remodelling with excessive deposition of extracellular matrix (ECM) and larger smooth muscle mass are correlated with increased airway responsiveness and asthma severity. Calpain is a family of calcium-dependent endopeptidases, which plays an important role in ECM remodelling. However, the role of calpain in airway smooth muscle remodelling remains unknown. OBJECTIVE: To investigate the role of calpain in asthmatic airway remodelling as well as the underlying mechanism...
September 20, 2016: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
Xiao-Yu Zhang, Luo-Xian Zhang, Cui-Jie Tian, Xue-Yi Tang, Li-Min Zhao, Ya-Li Guo, Dong-Jun Cheng, Xian-Liang Chen, Li-Jun Ma, Zhuo-Chang Chen
BACKGROUND: Long noncoding RNAs (lncRNAs) played important roles in several biological processes through regulating the expression of protein. However, the function of lncRNA BCYRN1 in airway smooth muscle cells (ASMCs) has not been reported. METHODS: Male Sprague-Dawley (SD) rats were divided into control and asthma groups and the ovalbumin (OVA) model was constructed. The expression of BCYRN1 and transient receptor potential 1 (TRPC1) were detected in the ASMCs separated from these rats...
2016: American Journal of Translational Research
Soojin Park, Hwan-Suck Chung, Dasom Shin, Kyung-Hwa Jung, Hyunil Lee, Junghee Moon, Hyunsu Bae
Foxp3 is a master regulator of CD4(+)CD25(+) regulatory T-cell (Treg) function and is also a suppressor of SKP2 and HER2/ErbB2. There are an increasing number of reports describing the functions of Foxp3 in cell types other than Tregs. In this context, we evaluated the functions of Foxp3 in ovalbumin- and cockroach-induced asthma models. Foxp3-EGFP-expressing adenovirus or EGFP control adenovirus was administered intratracheally (i.t.), followed by challenge with ovalbumin (OVA) or cockroach extract to induce asthma...
September 16, 2016: Experimental & Molecular Medicine
Tim Koopmans, Stijn Crutzen, Mark H Menzen, Andrew J Halayko, Tillie-Louise Hackett, Darryl A Knight, Reinoud Gosens
BACKGROUND AND PURPOSE: Asthma is a heterogeneous chronic inflammatory disease, characterized by the development of structural changes (airway remodelling). β-catenin, a transcriptional co-activator is fundamentally involved in airway smooth muscle growth, and may be a potential target in the treatment of airway smooth muscle remodelling. EXPERIMENTAL APPROACH: Using small-molecule compounds that selectively target β-catenin breakdown or its interactions with transcriptional co-activators, we assessed their ability to inhibit airway smooth muscle remodelling in vitro and in vivo...
September 15, 2016: British Journal of Pharmacology
Chao Wang, Qingfa Liu, Fangfang Chen, Wenjuan Xu, Caiqing Zhang, Wei Xiao
BACKGROUND: Interleukin-25 (IL-25) is a potent activator of type-2 immune responses, and is responsible for airway inflammation in asthma. Previous reports have shown that IL-25 expressed hyper-reactivity in an experimental mouse-model of asthma. In addition, the production of IL-13/IL-5 promoted by nuocytes induced airway inflammation. Thus, it has been questioned whether blocking IL-25 against its receptor IL-17BR could inhibit the expression of IL-13 and IL-5 via nuocytes, and further protect against inflammation in ovalbumin (OVA) induced mouse-model of asthma...
2016: PloS One
Georgina González-Avila, Blanca Bazan-Perkins, Cuauhtémoc Sandoval, Bettina Sommer, Sebastian Vadillo-Gonzalez, Carlos Ramos, Arnoldo Aquino-Galvez
Asthma airway remodeling is characterized by the thickening of the basement membrane (BM) due to an increase in extracellular matrix (ECM) deposition, which contributes to the irreversibility of airflow obstruction. Interstitial collagens are the primary ECM components to be increased during the fibrotic process. The aim of the present study was to examine the interstitial collagen turnover during the course of acute and chronic asthma, and 1 month after the last exposure to the allergen. Guinea pigs sensitized to ovalbumin (OVA) and exposed to 3 further OVA challenges (acute model) or 12 OVA challenges (chronic model) were used as asthma experimental models...
September 2016: Experimental and Therapeutic Medicine
Liang-Ti Huang, Hsuen-Wen Chang, Min-Ju Wu, Yong-Tzuo Lai, Wen-Chi Wu, Winston C Y Yu, Vincent H S Chang
KLF10 is a transforming growth factor (TGF)-β/Smad downstream regulated gene. KLF10 binds to the promoter of target genes and mimics the effects of TGF-β as a transcriptional factor. In our laboratory, we noted that Klf10 deficiency in mice is associated with significant inflammation of the lungs. However, the precise mechanism of this association remains unknown. We previously identified NPRA as a target gene potentially regulated by KLF10 through direct binding; NPRA knockout have known that prevented lung inflammation in a mouse model of allergic asthma...
October 2016: International Journal of Biochemistry & Cell Biology
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