The traditional herbal formulation, Jianpiyifei II, reduces pulmonary inflammation induced by influenza A virus and cigarette smoke in mice

Chronic obstructive pulmonary disease (COPD) is a worldwide chronic inflammatory lung disease, and influenza A virus (IAV) infection is a common cause of acute exacerbations of COPD (AECOPD). Therefore, targeting viral infections represents a promising strategy to prevent the occurrence and development of inflammatory flare ups in AECOPD. Jianpiyifei II (JPYFII) is a traditional herbal medicine used in China to treat patients with COPD, and its clinical indications are not well understood. However, investigation of the anti-inflammatory effects and underlying mechanism using an animal model of smoking has been reported in a previous study by our group. In addition, some included herbs, such as Radix astragali and Radix aupleuri, were reported to exhibit anti-viral effects. Therefore, the aim of this study was to investigate whether JPYFII formulation relieved acute inflammation by clearing the IAV in a mouse model that was exposed to cigarette smoke experimentally. JPYFII formulation treatment during smoke exposure and IAV infection significantly reduced the number of cells observed in bronchoalveolar lavage fluid (BALF), expression of pro-inﬂammatory cytokines, chemokines, superoxide production, and viral load in IAV-infected and smoke-exposed mice. However, JPYFII formulation treatment during smoke exposure alone did not reduce the number of cells in BALF or the expression of Il-6, Tnf-a, and Il-1β. The results demonstrated that JPYFII formulation exerted an anti-viral effect and reduced the exacerbation of lung inflammation in cigarette smoke (CS)-exposed mice infected with IAV. Our results suggested that JPYFII formulation could potentially be used to treat patients with AECOPD associated with IAV infection.

Download Full-text

Galgeun-tang Attenuates Cigarette Smoke and Lipopolysaccharide Induced Pulmonary Inflammation via IκBα/NF-κB Signaling

Molecules ◽

10.3390/molecules23102489 ◽

2018 ◽

Vol 23 (10) ◽

pp. 2489 ◽

Cited By ~ 6

Author(s):

Na-Rae Shin ◽

Chul Kim ◽

Chang-Seob Seo ◽

Je-Won Ko ◽

Young-Kwon Cho ◽

...

Keyword(s):

Cigarette Smoke ◽

Inflammatory Cell ◽

Pulmonary Inflammation ◽

Water Extract ◽

Lavage Fluid ◽

Chronic Obstructive ◽

Necrosis Factor Alpha ◽

Obstructive Pulmonary Disease ◽

Cell Counts ◽

Oxide Synthase

Galgeun-tang water extract (GGWE) is used to treat various diseases such as the common cold, eczema and asthma in China and Korea. In this study, we investigated the anti-inflammatory effect of GGWE using a cigarette smoke (CS)- and lipopolysaccharide (LPS)-induced induced pulmonary inflammation mouse model. The mice were exposed to CS for a total of seven days (eight cigarettes per day for 1 h) and LPS was administered intranasally to mice on day 4. GGWE was administered by oral gavage at doses of 50 mg/kg or 100 mg/kg 1 h before exposure to CS. GGWE decreased inflammatory cell counts, and expression of inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α) in bronchoalveolar lavage fluid (BALF) from mice exposed to CS and LPS. GGWE reduced the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), as well as the phosphorylation of inhibitor of kappa-B subunit alpha (IκBα) and nuclear factor kappa-B (NF-κB) in CS- and LPS-exposed mice. Histological examinations revealed that GGWE suppressed inflammatory cell infiltration into lung tissue compared to untreated CS- and LPS-exposed mice. In conclusion, GGWE effectively suppressed CS- and LPS-induced pulmonary inflammation. Our results indicate that GGWE may be used as a protective drug to control pulmonary inflammation diseases such as chronic obstructive pulmonary disease.

Download Full-text

Pneumocystis murina Infection and Cigarette Smoke Exposure Interact To Cause Increased Organism Burden, Development of Airspace Enlargement, and Pulmonary Inflammation in Mice

Infection and Immunity ◽

10.1128/iai.00165-08 ◽

2008 ◽

Vol 76 (8) ◽

pp. 3481-3490 ◽

Cited By ~ 34

Author(s):

Paul J. Christensen ◽

Angela M. Preston ◽

Tony Ling ◽

Ming Du ◽

W. Bradley Fields ◽

...

Keyword(s):

Cigarette Smoke ◽

Pulmonary Inflammation ◽

Airflow Obstruction ◽

Smoke Exposure ◽

Cigarette Smoke Exposure ◽

Chronic Obstructive ◽

Respiratory Pathogens ◽

Obstructive Pulmonary Disease ◽

Immunocompetent Mice

ABSTRACT Chronic obstructive pulmonary disease (COPD) is characterized by the presence of airflow obstruction and lung destruction with airspace enlargement. In addition to cigarette smoking, respiratory pathogens play a role in pathogenesis, but specific organisms are not always identified. Recent reports demonstrate associations between the detection of Pneumocystis jirovecii DNA in lung specimens or respiratory secretions and the presence of emphysema in COPD patients. Additionally, human immunodeficiency virus-infected individuals who smoke cigarettes develop early emphysema, but a role for P. jirovecii in pathogenesis remains speculative. We developed a new experimental model using immunocompetent mice to test the interaction of cigarette smoke exposure and environmentally acquired Pneumocystis murina infection in vivo. We hypothesized that cigarette smoke and P. murina would interact to cause increases in total lung capacity, airspace enlargement, and pulmonary inflammation. We found that exposure to cigarette smoke significantly increases the lung organism burden of P. murina. Pulmonary infection with P. murina, combined with cigarette smoke exposure, results in changes in pulmonary function and airspace enlargement characteristic of pulmonary emphysema. P. murina and cigarette smoke exposure interact to cause increased lung inflammatory cell accumulation. These findings establish a novel animal model system to explore the role of Pneumocystis species in the pathogenesis of COPD.

Download Full-text

Treating Viral Exacerbations Of COPD With Steroids: Lessons Learned From Animal Models Of Cigarette Smoke Exposure And Influenza A Virus Infection

10.1164/ajrccm-conference.2010.181.1_meetingabstracts.a1016 ◽

2010 ◽

Author(s):

Carla M. Bauer ◽

Caleb C. Zavitz ◽

Kristen N. Lambert ◽

Earl G. Brown ◽

Karen L. Mossman ◽

...

Keyword(s):

Animal Models ◽

Virus Infection ◽

Cigarette Smoke ◽

Influenza A Virus ◽

Influenza A ◽

Smoke Exposure ◽

Lessons Learned ◽

Cigarette Smoke Exposure ◽

Influenza A Virus Infection

Download Full-text

FSTL1 aggravates cigarette smoke-induced airway inflammation and airway remodeling by regulating autophagy

BMC Pulmonary Medicine ◽

10.1186/s12890-021-01409-6 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Ying Liu ◽

Jiawei Xu ◽

Tian Liu ◽

Jinxiang Wu ◽

Jiping Zhao ◽

...

Keyword(s):

Lung Function ◽

Airway Inflammation ◽

Cigarette Smoke ◽

Airway Remodeling ◽

Critical Factor ◽

Lavage Fluid ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Copd Patients ◽

Impaired Lung Function

Abstract Background Cigarette smoke (CS) is a major risk factor for Chronic Obstructive Pulmonary Disease (COPD). Follistatin-like protein 1 (FSTL1), a critical factor during embryogenesis particularly in respiratory lung development, is a novel mediator related to inflammation and tissue remodeling. We tried to investigate the role of FSTL1 in CS-induced autophagy dysregulation, airway inflammation and remodeling. Methods Serum and lung specimens were obtained from COPD patients and controls. Adult female wild-type (WT) mice, FSTL1± mice and FSTL1flox/+ mice were exposed to room air or chronic CS. Additionally, 3-methyladenine (3-MA), an inhibitor of autophagy, was applied in CS-exposed WT mice. The lung tissues and serum from patients and murine models were tested for FSTL1 and autophagy-associated protein expression by ELISA, western blotting and immunohistochemical. Autophagosome were observed using electron microscope technology. LTB4, IL-8 and TNF-α in bronchoalveolar lavage fluid of mice were examined using ELISA. Airway remodeling and lung function were also assessed. Results Both FSTL1 and autophagy biomarkers increased in COPD patients and CS-exposed WT mice. Autophagy activation was upregulated in CS-exposed mice accompanied by airway remodeling and airway inflammation. FSTL1± mice showed a lower level of CS-induced autophagy compared with the control mice. FSTL1± mice can also resist CS-induced inflammatory response, airway remodeling and impaired lung function. CS-exposed WT mice with 3-MA pretreatment have a similar manifestation with CS-exposed FSTL1± mice. Conclusions FSTL1 promotes CS-induced COPD by modulating autophagy, therefore targeting FSTL1 and autophagy may shed light on treating cigarette smoke-induced COPD.

Download Full-text

Acute non-atopic late-onset asthma induced by respiratory infection

Russian Pulmonology ◽

10.18093/0869-0189-2005-0-1-53-57 ◽

2005 ◽

pp. 53-57

Author(s):

S. A. Sobchenko ◽

O. S. Schetchikova ◽

N. V. Yakovleva

Keyword(s):

Respiratory Infection ◽

Influenza A ◽

Viral Infections ◽

Late Onset ◽

Lavage Fluid ◽

Atopic Asthma ◽

Influenza A Viruses ◽

Asthma Patients ◽

Bacterial Associations ◽

Autumn And Winter

The aim of the study was to investigate features of respiratory infection inducing acute non-atopic late-onset asthma (NLA). Virologic and microbiologic examinations of brash biopsy samples of rhinopharyngeal and bronchial mucosa and bronchial lavage fluid were performed in 116 NLA patients admitted to a hospital in autumn and winter. The leading cause of acute NLA was found to be respiratory viral infections. We noted that different clinical NLA types had different sensibility to various viruses: adenoviruses mainly caused exacerbations of aspirin-induced asthma, respiratory syncytial and influenza A viruses were prevalently determined in non-atopic asthma. Patients with posttuberculotic lesions of the lungs mostly had viral and bacterial associations. Such mixed infection resulted in more severe and prolonged exacerbations of NLA.

Download Full-text

Matrine reduces cigarette smoke-induced airway neutrophilic inflammation by enhancing neutrophil apoptosis

Clinical Science ◽

10.1042/cs20180912 ◽

2019 ◽

Vol 133 (4) ◽

pp. 551-564 ◽

Cited By ~ 9

Author(s):

Xuhua Yu ◽

Huei Jiunn Seow ◽

Hao Wang ◽

Desiree Anthony ◽

Steven Bozinovski ◽

...

Keyword(s):

Cigarette Smoke ◽

Lung Inflammation ◽

Therapeutic Potential ◽

Proteolytic Enzymes ◽

Ex Vivo ◽

Lavage Fluid ◽

Airflow Limitation ◽

Chronic Obstructive ◽

Neutrophilic Inflammation ◽

Anti Inflammatory

AbstractChronic Obstructive Pulmonary Disease (COPD) is a major incurable global health burden and will become the third largest cause of death in the world by 2030. It is well established that an exaggerated inflammatory and oxidative stress response to cigarette smoke (CS) leads to, emphysema, small airway fibrosis, mucus hypersecretion, and progressive airflow limitation. Current treatments have limited efficacy in inhibiting chronic inflammation and consequently do not reverse the pathology that initiates and drives the long-term progression of disease. In particular, there are no effective therapeutics that target neutrophilic inflammation in COPD, which is known to cause tissue damage by degranulation of a suite of proteolytic enzymes including neutrophil elastase (NE). Matrine, an alkaloid compound extracted from Sophora flavescens Ait, has well known anti-inflammatory activity. Therefore, the aim of the present study was to investigate whether matrine could inhibit CS-induced lung inflammation in mice. Matrine significantly reduced CS-induced bronchoalveolar lavage fluid (BALF) neutrophilia and NE activity in mice. The reduction in BALF neutrophils in CS-exposed mice by matrine was not due to reductions in pro-neutrophil cytokines/chemokines, but rather matrine’s ability to cause apoptosis of neutrophils, which we demonstrated ex vivo. Thus, our data suggest that matrine has anti-inflammatory actions that could be of therapeutic potential in treating CS-induced lung inflammation observed in COPD.

Download Full-text

Curcumin attenuates elastase- and cigarette smoke-induced pulmonary emphysema in mice

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.90443.2008 ◽

2009 ◽

Vol 296 (4) ◽

pp. L614-L623 ◽

Cited By ~ 60

Author(s):

Masaru Suzuki ◽

Tomoko Betsuyaku ◽

Yoko Ito ◽

Katsura Nagai ◽

Nao Odajima ◽

...

Keyword(s):

Bronchoalveolar Lavage ◽

Cigarette Smoke ◽

Pulmonary Emphysema ◽

Bronchoalveolar Lavage Fluid ◽

Pulmonary Inflammation ◽

Antioxidant Properties ◽

Lavage Fluid ◽

Curcumin Treatment ◽

Air Space ◽

Antioxidant Gene Expression

Curcumin, a yellow pigment obtained from turmeric ( Curcumina longa), is a dietary polyphenol that has been reported to possess anti-inflammatory and antioxidant properties. The effect of curcumin against the development of pulmonary emphysema in animal models is unknown. The aim of this study was to determine whether curcumin is able to attenuate the development of pulmonary emphysema in mice. Nine-week-old male C57BL/6J mice were treated with intratracheal porcine pancreatic elastase (PPE) or exposed to mainstream cigarette smoke (CS) (60 min/day for 10 consecutive days or 5 days/wk for 12 wk) to induce pulmonary inflammation and emphysema. Curcumin (100 mg/kg) or vehicle was administrated daily by oral gavage 1 h and 24 h before intratracheal PPE treatment and daily thereafter throughout a 21-day period in PPE-exposed mice and 1 h before each CS exposure in CS-exposed mice. As a result, curcumin treatment significantly inhibited PPE-induced increase of neutrophils in bronchoalveolar lavage fluid at 6 h and on day 1 after PPE administration, with an increase in antioxidant gene expression at 6 h and significantly attenuated PPE-induced air space enlargement on day 21. It was also found that curcumin treatment significantly inhibited CS-induced increase of neutrophils and macrophages in bronchoalveolar lavage fluid after 10 consecutive days of CS exposure and significantly attenuated CS-induced air space enlargement after 12 wk of CS exposure. In conclusion, oral curcumin administration attenuated PPE- and CS-induced pulmonary inflammation and emphysema in mice.

Download Full-text

Chronic Cigarette Smoke Exposure Primes NK Cell Activation in a Mouse Model of Chronic Obstructive Pulmonary Disease

The Journal of Immunology ◽

10.4049/jimmunol.0903654 ◽

2010 ◽

Vol 184 (8) ◽

pp. 4460-4469 ◽

Cited By ~ 51

Author(s):

Gregory T. Motz ◽

Bryan L. Eppert ◽

Brian W. Wortham ◽

Robyn M. Amos-Kroohs ◽

Jennifer L. Flury ◽

...

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Mouse Model ◽

Pulmonary Disease ◽

Cigarette Smoke ◽

Cell Activation ◽

Nk Cell ◽

Smoke Exposure ◽

Cigarette Smoke Exposure ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease

Download Full-text

Total particulate matter concentration skews cigarette smoke's gene expression profile

ERJ Open Research ◽

10.1183/23120541.00029-2016 ◽

2016 ◽

Vol 2 (4) ◽

pp. 00029-2016 ◽

Cited By ~ 5

Author(s):

Anna Dvorkin-Gheva ◽

Gilles Vanderstocken ◽

Ali Önder Yildirim ◽

Corry-Anke Brandsma ◽

Ma'en Obeidat ◽

...

Keyword(s):

Gene Expression ◽

Particulate Matter ◽

Cigarette Smoke ◽

Gene Expression Profile ◽

Expression Profile ◽

Smoke Exposure ◽

Cigarette Smoke Exposure ◽

Chronic Obstructive ◽

Total Particulate Matter ◽

Xenobiotic Detoxification

Exposure of small animals to cigarette smoke is widely used as a model to study the pathogenesis of chronic obstructive pulmonary disease. However, protocols and exposure systems utilised vary substantially and it is unclear how these different systems compare.We analysed the gene expression profile of six publically available murine datasets from different cigarette smoke-exposure systems and related the gene signatures to three clinical cohorts.234 genes significantly regulated by cigarette smoke in at least one model were used to construct a 55-gene network containing 17 clusters. Increasing numbers of differentially regulated clusters were associated with higher total particulate matter concentrations in the different datasets. Low total particulate matter-induced genes mainly related to xenobiotic/detoxification responses, while higher total particulate matter activated immune/inflammatory processes in addition to xenobiotic/detoxification responses. To translate these observations to the clinic, we analysed the regulation of the revealed network in three human cohorts. Similar to mice, we observed marked differences in the number of regulated clusters between the cohorts. These differences were not determined by pack-year.Although none of the experimental models exhibited a complete alignment with any of the human cohorts, some exposure systems showed higher resemblance. Thus, depending on the cohort, clinically observed changes in gene expression may be mirrored more closely by specific cigarette smoke exposure systems. This study emphasises the need for careful validation of animal models.

Download Full-text