Toll-like receptor 4 antagonist (E5564) prevents the chronic airway response to inhaled lipopolysaccharide

Savov, Jordan D.; Brass, David M.; Lawson, Barbara L.; McElvania-Tekippe, Erin; Walker, Julia K. L.; Schwartz, David A.

doi:10.1152/ajplung.00014.2005

Cited by 71 publications

(52 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, LPS may play an important role in bacterial infection-induced exacerbations of COPD, which contribute to the progression of the disease [28]. Accordingly, in various animal models, inhalation of LPS was shown to induce pathological features of COPD, such as neutrophilia, goblet cell hyperplasia, airway fibrosis and emphysema [29][30][31][32]. In the present study, we present evidence that ACh plays a major role in the development of pulmonary inflammation as well as in airway remodelling.…”

mentioning

confidence: 49%

Tiotropium inhibits pulmonary inflammation and remodelling in a guinea pig model of COPD

Pera¹,

Zuidhof²,

Valadas³

et al. 2011

European Respiratory Journal

113

View full text Add to dashboard Cite

Airway remodelling and emphysema are major structural abnormalities in chronic obstructive pulmonary disease (COPD). In addition, pulmonary vascular remodelling may occur and contribute to pulmonary hypertension, a comorbidity of COPD. Increased cholinergic activity in COPD contributes to airflow limitation and, possibly, to inflammation and airway remodelling.This study aimed to investigate the role of acetylcholine in pulmonary inflammation and remodelling using an animal model of COPD. To this aim, guinea pigs were instilled intranasally with lipopolysaccharide (LPS) twice weekly for 12 weeks and were treated, by inhalation, with the long-acting muscarinic receptor antagonist tiotropium.Repeated LPS exposure induced airway and parenchymal neutrophilia, and increased goblet cell numbers, lung hydroxyproline content, airway wall collagen and airspace size. Furthermore, LPS increased the number of muscularised microvessels in the adventitia of cartilaginous airways. Tiotropium abrogated the LPS-induced increase in neutrophils, goblet cells, collagen deposition and muscularised microvessels, but had no effect on emphysema.In conclusion, tiotropium inhibits remodelling of the airways as well as pulmonary inflammation in a guinea pig model of COPD, suggesting that endogenous acetylcholine plays a major role in the pathogenesis of this disease.

show abstract

mentioning

confidence: 49%

Tiotropium inhibits pulmonary inflammation and remodelling in a guinea pig model of COPD

Pera¹,

Zuidhof²,

Valadas³

et al. 2011

European Respiratory Journal

113

View full text Add to dashboard Cite

show abstract

“…Furthermore, the nature of the LPS in OVA has been reported to have some features in common with Salmonella LPS (40); that may have some account for differences from Pseudomonas LPS. To explore the effects of LPS exposure on the respiratory system, a number of studies have used LPS from different sources such as Salmonella (24,40), Escherichia coli (E. coli) (7,9), and Pseudomonas (26,29,43). Lipid A has been recognized as the active portion responsible for most LPSinduced biological effects.…”

Section: L60 the Role Of Lps In Ova-induced Airway Remodelingmentioning

confidence: 99%

“…On the other hand, LPS inhalation by itself induces airway inflammation, AHR, and even collagen deposition, effects that are inhibited by a TLR4 antagonist (26). Some forms of LPS may also activate the epidermal growth factor receptor (EGFR) on airway epithelium through the release of transforming growth factor (TGF)-␣ and cause epithelial differentiation to goblet cells (14).…”

mentioning

confidence: 99%

The presence of LPS in OVA inhalations affects airway inflammation and AHR but not remodeling in a rodent model of asthma

Tsuchiya

Siddiqui

Risse

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

Tsuchiya K, Siddiqui S, Risse P-A, Hirota N, Martin JG. The presence of LPS in OVA inhalations affects airway inflammation and AHR but not remodeling in a rodent model of asthma. Am J Physiol Lung Cell Mol Physiol 303: L54 -L63, 2012. First published April 20, 2012 doi:10.1152/ajplung.00208.2011 is the most frequently used allergen in animal models of asthma. Lipopolysaccharide (LPS) contaminating commercial OVA may modulate the evoked airway inflammatory response to OVA. However, the effect of LPS in OVA on airway remodeling, especially airway smooth muscle (ASM) has not been evaluated. We hypothesized that LPS in commercial OVA may enhance allergen-induced airway inflammation and remodeling. Brown Norway rats were sensitized with OVA on day 0. PBS, OVA, or endotoxin-free OVA (Ef-OVA) was instilled intratracheally on days 14,19,24. Bronchoalveolar lavage (BAL) fluid, lung, and intrathoracic lymph node tissues were collected 48 h after the last challenge. Immunohistochemistry for ␣-smooth muscle actin, Periodic-Acid-Schiff staining, and real-time qPCR were performed. Airway hyperresponsiveness (AHR) was also measured. BAL fluid macrophages, eosinophils, neutrophils, and lymphocytes were increased in OVA-challenged animals, and macrophages and neutrophils were significantly lower in Ef-OVA-challenged animals. The ASM area in larger airways was significantly increased in both OVA and Ef-OVA compared with PBS-challenged animals. The mRNA expression of IFN-␥ and IL-13 in lung tissues and IL-4 in lymph nodes was significantly increased by both OVA and Ef-OVA compared with PBS and were not significantly different between OVA and Ef-OVA. Monocyte chemoattractant protein (MCP)-1 in BAL fluid and AHR were significantly increased in OVA but not in Ef-OVA. LPS contamination in OVA contributes to the influx of macrophages and MCP-1 increase in the airways and to AHR after OVA challenges but does not affect OVA-induced Th1 and Th2 cytokine expression, goblet cell hyperplasia, and ASM remodeling. animal model; airway hyperresponsiveness; Brown Norway rat; endotoxin; ovalbumin LIPOPOLYSACCHARIDE (LPS) is a cell wall component of Gramnegative bacteria and ubiquitous in the environment and is often present in polluted air as well as in household dust. There has been substantial interest in LPS for its effects on respiratory immunity since the development of the hygiene hypothesis (32, 38). Toll-like receptor 4 (TLR4) is a receptor for LPS, and activation of TLR4 is required to prime dendritic cells and epithelial cells for optimal responses to antigen exposure (12). Stimulation of TLR4 is essential for downstream cellular events that are mediated by mitogen-activated protein kinase p38 and c-Jun NH2-terminal kinase, leading to nuclear translocation of NF-B, resulting in cytokine mRNA transcription and release of proinflammatory cytokines (37).Ovalbumin (OVA) is widely used in animal models of asthma to study mechanisms of airway inflammation, airway hyperresponsiveness (AHR), and airway remodeling. However, commercial OVA has ...

show abstract

“…Lyophilized LPS (Escherichia coli 0111:B4, Sigma, St. Louis, MO) was used. For LPS aerosol generation, we used a six-jet Atomizer (TSI Inc., Shoreview, MN) at 35 psi as previously described (7). LPS aerosol concentrations in these experiments were 6-8 μg/m 3 .…”

Section: Lps Exposuresmentioning

confidence: 99%

Alloimmune Lung Injury Induced by Local Innate Immune Activation Through Inhaled Lipopolysaccharide

et al. 2007

Self Cite

View full text Add to dashboard Cite

Background-Alloimmune lung injury, characterized by perivascular lymphocytic inflammation, lymphocytic bronchiolitis (LB), and obliterative bronchiolitis (OB), causes substantial morbidity and mortality after lung transplantation and bone marrow transplantation (BMT), but little is known regarding its pathogenesis. We have developed and pursued the hypothesis that local activation of pulmonary innate immunity through toll-like receptor (TLR)-4 is critical to the development of posttransplant alloimmune lung injury.

show abstract

Toll-like receptor 4 antagonist (E5564) prevents the chronic airway response to inhaled lipopolysaccharide

Abstract: Toll-like receptor 4 antagonist (E5564) prevents the chronic airway response to inhaled lipopolysaccharide.

Cited by 71 publications

References 32 publications

Tiotropium inhibits pulmonary inflammation and remodelling in a guinea pig model of COPD

Tiotropium inhibits pulmonary inflammation and remodelling in a guinea pig model of COPD

The presence of LPS in OVA inhalations affects airway inflammation and AHR but not remodeling in a rodent model of asthma

Alloimmune Lung Injury Induced by Local Innate Immune Activation Through Inhaled Lipopolysaccharide

Contact Info

Product

Resources

About