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Mouse emphysema

Milena V Oliveira, Soraia C Abreu, Gisele A Padilha, Nazareth N Rocha, Lígia A Maia, Christina M Takiya, Debora G Xisto, Bela Suki, Pedro L Silva, Patricia R M Rocco
Many experimental models have been proposed to study the pathophysiological features of emphysema, as well as to search for new therapeutic approaches for acute or chronically injured lung parenchyma. We aimed to characterize an emphysema model induced by multiple instillations of elastase by tracking changes in inflammation, remodeling, and cardiac function after each instillation. Forty-eight C57BL/6 mice were randomly assigned across two groups. Emphysema (ELA) animals received 1, 2, 3, or 4 intratracheal instillations of pancreatic porcine elastase (PPE, 0...
2016: Frontiers in Physiology
Yoonki Hong, You-Sun Kim, Seok-Ho Hong, Yeon-Mok Oh
There is no therapy currently available that influences the natural history of disease progression in patients with chronic obstructive pulmonary disease (COPD). Although stem cell therapy is considered a potential therapeutic option in COPD, there are no clinical trials proving definitive therapeutic effects in patients with COPD. Recently, it was reported that pioglitazone might potentiate the therapeutic effects of stem cells in patients with heart or liver disease. To test the capacity of pioglitazone pretreatment of stem cells for emphysema repair, we evaluated the therapeutic effects of pioglitazone-pretreated human adipose-derived mesenchymal stem cells (ASCs) on elastase-induced or cigarette smoke-induced emphysema in mice...
October 21, 2016: Experimental & Molecular Medicine
RyeonJin Cho, You-Sun Kim, Ji-Young Kim, Yeon-Mok Oh
BACKGROUND/PURPOSE: Emphysema, a pathologic component of chronic obstructive pulmonary disease, causes irreversible destruction. Many researchers have reported that mesenchymal stem cells can regenerate lung tissue after emphysema. METHODS: We evaluated if spheroid human adipose-derived mesenchymal stem cells (ASCs) showed greater regenerative effects than dissociated ASCs in elastase-induced emphysema mice. ASCs were administered via an intrapleural route. RESULTS: Mice injected with spheroid ASCs showed improved regeneration of lung tissue, increased expression of growth factors such as FGF2 and HGF, and a reduction in proteases with an induction of protease inhibitors when compared with mice injected with dissociated ASCs...
October 19, 2016: BMB Reports
Mamoru Sasaki, Shotaro Chubachi
The features of chronic obstructive pulmonary disease(COPD)are chronic inflammatory and emphysema changes in the lungs by long-term cigarette smoke(CS)exposure. Osteoporosis is an important systemic comorbidity of COPD. Severe emphysema and low body mass index(BMI)are independent risk factors for low bone mineral density in COPD patients. However the pathophysiologic mechanisms underlying emphysema and osteoporosis have not been fully elucidated. An established mouse model of CS-induced emphysema with decrease body weight and bone mineral density is important for investigating the cause of osteoporosis in COPD patients...
2016: Clinical Calcium
Koh Uyama, Shoji Sakiyama, Mitsuteru Yoshida, Koichiro Kenzaki, Hiroaki Toba, Yukikiyo Kawakami, Kazumasa Okumura, Hiromitsu Takizawa, Kazuya Kondo, Akira Tangoku
The mortality and morbidity of chronic obstructive pulmonary disease are high. However, no radical therapy has been developed to date. The purpose of this study was to evaluate whether fetal mouse lung tissue can grow and differentiate in the emphysematous lung. Fetal lung tissue from green fluorescent protein C57BL/6 mice at 16 days' gestation was used as donor material. Twelve-month-old pallid mice were used as recipients. Donor lungs were cut into small pieces and implanted into the recipient left lung by performing thoracotomy under anesthesia...
2016: Journal of Medical Investigation: JMI
Isabelle Meunier, Béatrice Bocquet, Gilles Labesse, Christina Zeitz, Sabine Defoort-Dhellemmes, Annie Lacroux, Martine Mauget-Faysse, Isabelle Drumare, Anne-Sophie Gamez, Cyril Mathieu, Virginie Marquette, Lola Sagot, Claire-Marie Dhaenens, Carl Arndt, Patrick Carroll, Martine Remy-Jardin, Salomon Yves Cohen, José-Alain Sahel, Bernard Puech, Isabelle Audo, Sarah Mrejen, Christian P Hamel
To revisit the autosomal dominant Sorsby fundus dystrophy (SFD) as a syndromic condition including late-onset pulmonary disease. We report clinical and imaging data of ten affected individuals from 2 unrelated families with SFD and carrying heterozygous TIMP3 mutations (c.572A > G, p.Y191C, exon 5, in family 1 and c.113C > G, p.S38C, exon 1, in family 2). In family 1, all SFD patients older than 50 (two generations) had also a severe emphysema, despite no history of smoking or asthma. In the preceding generation, the mother died of pulmonary emphysema and she was blind after the age of 50...
2016: Scientific Reports
Emanuel Kennedy-Feitosa, Renata Tiemi Okuro, Vanessa Pinho Ribeiro, Manuella Lanzetti, Marina Valente Barroso, Walter Araújo Zin, Luís Cristóvão Porto, Lycia Brito-Gittirana, Samuel Santos Valenca
Short-term cigarette smoke (CS) exposure does not cause emphysema; however, some pathogenesis hallmarks are maintained, such as oxidative stress and inflammation. This study aimed to test the efficacy of eucalyptol against short-term CS exposure in mice. C57BL/6 mice were exposed to 12 cigarettes per day for 5 days (CS group). The control group was exposed to sham smoking. Three groups of mice exposed to CS were treated to different concentrations of eucalyptol (1, 3, 10 mg/mL) via inhalation (15 min/daily) for 5 days (CS + 1 mg, CS+3 mg and CS+10 mg groups)...
September 3, 2016: Pulmonary Pharmacology & Therapeutics
Tanveer Ahmad, Isaac K Sundar, Ana M Tormos, Chad A Lerner, Janice Gerloff, Hongwei Yao, Irfan Rahman
Lung cellular senescence and inflammatory response are the key events in the pathogenesis of chronic obstructive pulmonary disease (COPD) where cigarette smoke (CS) is the main etiological factor. Telomere dysfunction is induced by either critical shortening or disruption of the shelterin complex, leading to cellular senescence. However, it remains unknown whether disruption of shelterin complex is responsible for CS-induced lung cellular senescence. Here we show that TPP1 levels are reduced on telomeres in mouse lungs with emphysema, as well as in lungs from smokers and COPD patients...
August 25, 2016: American Journal of Respiratory Cell and Molecular Biology
Daniel Hernández-Saavedra, Linda Sanders, Mario J Perez, Beata Kosmider, Lynelle P Smith, John D Mitchell, Toshinori Yoshida, Rubin M Tuder
Tobacco smoke (TS) causes chronic obstructive pulmonary disease including, chronic bronchitis, emphysema and asthma. Rtp801, an inhibitor of mTORC1, is induced by oxidative stress triggered by TS. Its upregulation drives lung susceptibility to TS injury by means of enhancing inflammation and alveolar destruction. We postulated that Rtp801 is not only increased by reactive oxygen species (ROS) in TS, but it is instrumental in creating a feedforward process leading to amplification of endogenous ROS generation...
August 24, 2016: American Journal of Respiratory Cell and Molecular Biology
Anna Salazar-Degracia, David Blanco, Mònica Vilà-Ubach, Gabriel de Biurrun, Carlos Ortiz de Solórzano, Luis M Montuenga, Esther Barreiro
BACKGROUND: Muscle wasting negatively impacts the progress of chronic diseases such as lung cancer (LC) and emphysema, which are in turn interrelated. OBJECTIVES: We hypothesized that muscle atrophy and body weight loss may develop in an experimental mouse model of lung carcinogenesis, that the profile of alterations in muscle fiber phenotype (fiber type composition and morphometry, muscle structural alterations, and nuclear apoptosis), and in muscle metabolism are similar in both respiratory and limb muscles of the tumor-bearing mice, and that the presence of underlying emphysema may influence those events...
2016: Journal of Translational Medicine
Marilyn K Glassberg, Paola Catanuto, Shahriar Shahzeidi, Muddassir Aliniazee, Sarit Lilo, Gustavo A Rubio, Sharon J Elliot
Female smokers have a faster decline in lung function with increasing age and overall develop a greater loss of lung function than male smokers. This raises the question of whether estrogen status in women affects susceptibility to cigarette smoke (CS)-induced lung disease. Mouse models suggest that female mice are more susceptible than males to CS-induced lung disease. Moreover, young CS-exposed female mice develop emphysema earlier than male mice. The purpose of this study was to characterize the relationship of estrogen status on the pattern and severity of CS-induced lung disease...
July 25, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
Tatsuhiko Harada, Yuji Ishimatsu, Atsuko Hara, Towako Morita, Shota Nakashima, Tomoyuki Kakugawa, Noriho Sakamoto, Kosuke Kosai, Koichi Izumikawa, Katsunori Yanagihara, Hiroshi Mukae, Shigeru Kohno
Secondary bacterial pneumonia (SBP) during influenza increases the severity of chronic obstructive pulmonary disease (COPD) and its associated mortality. Macrolide antibiotics, including clarithromycin (CAM), are potential treatments for a variety of chronic respiratory diseases owing to their pharmacological activities, in addition to antimicrobial action. We examined the efficacy of CAM for the treatment of SBP after influenza infection in COPD. Specifically, we evaluated the effect of CAM in elastase-induced emphysema mice that were inoculated with influenza virus (strain A/PR8/34) and subsequently infected with macrolide-resistant Streptococcus pneumoniae CAM was administered to the emphysema mice 4 days prior to influenza virus inoculation...
September 2016: Journal of Pharmacology and Experimental Therapeutics
Liang-Jian Kuang, Ting-Ting Deng, Qin Wang, Shi-Lin Qiu, Yi Liang, Zhi-Yi He, Jian-Quan Zhang, Jing Bai, Mei-Hua Li, Jing-Min Deng, Guang-Nan Liu, Ji-Feng Liu, Xiao-Ning Zhong
Dendritic cells and CD8(+) T cells participate in the pathology of chronic obstructive pulmonary disease, including emphysema, but little is known of the involvement of the CD40/CD40L pathway. We investigated the role of the CD40/CD40L pathway in Tc1 cell differentiation induced by dendritic cells in a mouse model of emphysema, and in vitro. C57BL/6J wild-type and CD40(-/-) mice were exposed to cigarette smoke (CS) or not (control), for 24 wk. In vitro experiments involved wild-type and CD40(-/-) dendritic cells treated with CS extract (CSE) or not...
September 1, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
Liu Liu, Xiangrong Geng, Joseph McDermott, Jian Shen, Cody Corbin, Stephanie Xuan, Jae Kim, Li Zuo, Zijuan Liu
Tumor necrosis factor (TNF)-α is a well-known pro-inflammatory cytokine. Increased expression of Tnf-α is a feature of inflammatory lung diseases, such as asthma, emphysema, fibrosis, and smoking-induced chronic obstructive pulmonary disease (COPD). Using a mouse line with lung-specific Tnf-α overexpression (SPC-TNF-α) to mimic TNF-α-associated lung diseases, we investigated the role of chronic inflammation in the homeostasis of lung trace elements. We performed a quantitative survey of micronutrients and biometals, including copper (Cu), zinc (Zn), and selenium (Se), in the transgenic mice tissues...
2016: Frontiers in Physiology
Saleela M Ruwanpura, Louise McLeod, Lovisa F Dousha, Huei J Seow, Sultan Alhayyani, Michelle D Tate, Virginie Deswaerte, Gavin D Brooks, Steven Bozinovski, Martin MacDonald, Christoph Garbers, Paul T King, Philip G Bardin, Ross Vlahos, Stefan Rose-John, Gary P Anderson, Brendan J Jenkins
RATIONALE: The potent immunomodulatory cytokine interleukin (IL)-6 is consistently upregulated in human lungs with emphysema, and in mouse emphysema models; however, the mechanism(s) by which IL-6 promotes emphysema remains obscure. IL-6 signals using two distinct modes, classical signalling via its membrane-bound IL-6 receptor (mIL-6R), and trans-signalling via a naturally-occurring soluble IL-6R (sIL-6R). OBJECTIVES: To identify whether IL-6 trans-signalling and/or classical signalling contribute to the pathogenesis of emphysema...
July 2, 2016: American Journal of Respiratory and Critical Care Medicine
Utako Fujii, Nobuaki Miyahara, Akihiko Taniguchi, Koichi Waseda, Daisuke Morichika, Etsuko Kurimoto, Hikari Koga, Mikio Kataoka, Erwin W Gelfand, Daniel J Cua, Akihiko Yoshimura, Mitsune Tanimoto, Arihiko Kanehiro
We recently reported that IL-17A plays a critical role in the development of porcine pancreatic elastase (PPE)-induced emphysema. The proliferation of T helper 17 (Th17) cells was induced by IL-23. To determine the contribution of IL-23 to the development of pulmonary emphysema a mouse model of PPE-induced emphysema was used in which responses of IL-23p19-deficient (IL-23-/-) and wild type (WT) mice were compared. Intra-tracheal instillation of PPE induced emphysematous changes in the lungs and was associated with increased levels of IL-23 in lung homogenates...
June 28, 2016: American Journal of Respiratory Cell and Molecular Biology
Shigemi Matsuyama, James Palmer, Adam Bates, Izmarie Poventud-Fuentes, Kelvin Wong, Justine Ngo, Mieko Matsuyama
Cells with DNA damage undergo apoptosis or cellular senescence if the damage cannot be repaired. Recent studies highlight that cellular senescence plays a major role in aging. However, age-associated diseases, including emphysema and neurodegenerative disorders, are caused by apoptosis of lung alveolar epithelial cells and neurons, respectively. Therefore, enhanced apoptosis also promotes aging and shortens the life span depending on the cell type. Recently, we reported that ku70(-) (/) (-)bax(-) (/) (-) and ku70(-) (/) (-)bax(+/) (-) mice showed significantly extended life span in comparison with ku70(-) (/) (-)bax(+/+) mice...
June 2016: Experimental Biology and Medicine
Robert F Foronjy, Matthias A Salathe, Abdoulaye J Dabo, Nathalie Baumlin, Neville Cummins, Edward Eden, Patrick Geraghty
The expression of Toll-like receptor (TLR)-9, a pathogen recognition receptor that recognizes unmethylated CpG sequences in microbial DNA molecules, is linked to the pathogenesis of several lung diseases. TLR9 expression and signaling was investigated in animal and cell models of chronic obstructive pulmonary disease (COPD). We observed enhanced TLR9 expression in mouse lungs following exposure to cigarette smoke. Tlr9(-/-) mice were resistant to cigarette smoke-induced loss of lung function as determined by mean linear intercept, total lung capacity, lung compliance, and tissue elastance analysis...
July 1, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
Giuseppe Lo Sasso, Walter K Schlage, Stéphanie Boué, Emilija Veljkovic, Manuel C Peitsch, Julia Hoeng
Atherosclerosis-prone apolipoprotein E-deficient (Apoe(-/-)) mice display poor lipoprotein clearance with subsequent accumulation of cholesterol ester-enriched particles in the blood, which promote the development of atherosclerotic plaques. Therefore, the Apoe(-/-) mouse model is well established for the study of human atherosclerosis. The systemic proinflammatory status of Apoe(-/-) mice also makes them good candidates for studying chronic obstructive pulmonary disease, characterized by pulmonary inflammation, airway obstruction, and emphysema, and which shares several risk factors with cardiovascular diseases, including smoking...
2016: Journal of Translational Medicine
Kyun Ha Kim, Hyuk-Hwan Song, Kyung-Seop Ahn, Sei-Ryang Oh, Ruxana T Sadikot, Myungsoo Joo
ETHNOPHARMACOLOGICAL RELEVANCE: The tuber of Alismataceae Alisma orientale Juzepzuk has been prescribed as a remedy for treating the diseases associated with body fluid dysfunction such as edema and inflammatory lung diseases. Chronic obstructive pulmonary disease (COPD) is a debilitating, inflammatory lung disease without effective treatment. Along with persistent inflammation, autophagy has been recently reported to contribute to COPD. Here, by employing a murine model, we examined whether the tuber of the plant is effective against COPD MATERIALS AND METHODS: The ethanol extract of the tuber of A...
July 21, 2016: Journal of Ethnopharmacology
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