Conditionally induced RAGE expression by proximal airway epithelial cells in transgenic mice causes lung inflammation

Bodine, B Garrett; Bennion, Brock G.; Leatham, Emma; Jimenez, Felix; Wright, Alex; Jergensen, Zac R; Erickson, Connor J; Jones, Carissa P; Johnson, Jeff P; Knapp, Steven M; Reynolds, Paul

doi:10.1186/s12931-014-0133-y

Cited by 12 publications

(11 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…HMGB1 and its receptor, receptors for advanced glycation end products (RAGE), are both upregulated in alveolar epithelial cells following cigarette smoke exposure (59). Expression of RAGE is also associated with increased lung inflammation (11). It is interesting that the RAGE ligand HMGB1 may inactivate nicotinic acetylcholine receptors in certain neuronal cells (14).…”

Section: Discussionmentioning

confidence: 99%

Acute pulmonary effects of aerosolized nicotine

Ahmad

Zafar

Mariappan

et al. 2019

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

Nicotine is a highly addictive principal component of both tobacco and electronic cigarette that is readily absorbed in blood. Nicotine-containing electronic cigarettes are promoted as a safe alternative to cigarette smoking. However, the isolated effects of inhaled nicotine are largely unknown. Here we report a novel rat model of aerosolized nicotine with a particle size (~1 μm) in the respirable diameter range. Acute nicotine inhalation caused increased pulmonary edema and lung injury as measured by enhanced bronchoalveolar lavage fluid protein, IgM, lung wet-to-dry weight ratio, and high-mobility group box 1 (HMGB1) protein and decreased lung E-cadherin protein. Immunohistochemical analysis revealed congested blood vessels and increased neutrophil infiltration. Lung myeloperoxidase mRNA and protein increased in the nicotine-exposed rats. Complete blood counts also showed an increase in neutrophils, white blood cells, eosinophils, and basophils. Arterial blood gas measurements showed an increase in lactate. Lungs of nicotine-inhaling animals revealed increased mRNA levels of IL-1A and CXCL1. There was also an increase in IL-1α protein. In in vitro air-liquid interface cultures of airway epithelial cells, there was a dose dependent increase in HMGB1 release with nicotine treatment. Air-liquid cultures exposed to nicotine also resulted in a dose-dependent loss of barrier as measured by transepithelial electrical resistance and a decrease in E-cadherin expression. Nicotine also caused a dose-dependent increase in epithelial cell death and an increase in caspase-3/7 activities. These results show that the nicotine content of electronic cigarettes may have adverse pulmonary and systemic effects.

show abstract

Section: Discussionmentioning

confidence: 99%

Acute pulmonary effects of aerosolized nicotine

Ahmad

Zafar

Mariappan

et al. 2019

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

show abstract

“…To measure the level of RAGE in the fixed lung sections, immunohistochemistry was performed by a method described by Bodine et al (27). The paraffin‐embedded sections were cut onto slides at preselected thicknesses of 4–6 μm, dewaxed with xylene, and dehydrated through a series of ethanols of cumulatively increased concentrations.…”

Section: Methodsmentioning

confidence: 99%

Blockade of RAGE ameliorates elastase‐induced emphysema development and progression via RAGE‐DAMP signaling

et al. 2017

View full text Add to dashboard Cite

The receptor for advanced glycan end products (RAGE) has been identified as a susceptibility gene for chronic obstructive pulmonary disease (COPD) in genome-wide association studies (GWASs). However, less is known about how RAGE is involved in the pathogenesis of COPD. To determine the molecular mechanism by which RAGE influences COPD in experimental COPD models, we investigated the efficacy of the RAGE-specific antagonist FPS-ZM1 administration in and COPD models. We injected elastase intratracheally and the RAGE antagonist FPS-ZM1 in mice, and the infiltrated inflammatory cells and cytokines were assessed by ELISA. Cellular expression of RAGE was determined in protein, serum, and bronchoalveolar lavage fluid of mice and lungs and serum of human donors and patients with COPD. Downstream damage-associated molecular pattern (DAMP) pathway activation and and in patients with COPD was assessed by immunofluorescence staining, Western blot analysis, and ELISA. The expression of membrane RAGE in initiating the inflammatory response and of soluble RAGE acting as a decoy were associated with up-regulation of the DAMP-related signaling pathway Nrf2. FPS-ZM1 administration significantly reversed emphysema in the lung of mice. Moreover, FPS-ZM1 treatment significantly reduced lung inflammation in , but not in mice. Thus, our data indicate for the first time that RAGE inhibition has an essential protective role in COPD. Our observation of RAGE inhibition provided novel insight into its potential as a therapeutic target in emphysema/COPD.-Lee, H., Park, J.-R., Kim, W. J., Sundar, I. K., Rahman, I., Park, S.-M., Yang. S.-R. Blockade of RAGE ameliorates elastase-induced emphysema development and progression RAGE-DAMP signaling.

show abstract

“…Its mRNA transcript level was increased in vitro in human T cells responding to alloantigen stimulation [24]. e IL-14, IL-17, and TNF-α level in whole lung homogenates were upregulated in RAGE transgenic mice [25]. Helen Kemp et al had demonstrated that the thyroid follicular cells in the thyroid had the ability to express IL-14 mRNA [26].…”

Section: Discussionmentioning

confidence: 99%

High TXLNA Expression Predicts Favourable Outcome for Pancreatic Adenocarcinoma Patients

Zhang

Xie

et al. 2020

BioMed Research International

View full text Add to dashboard Cite

TXLNA (taxilin alpha), a binding partner of the syntaxin family, was identified as a key factor in the coordination of intracellular vesicle trafficking and highly expressed in various tumor cells. However, the accurate relation between TXLNA and tumorigenesis and progression of pancreatic adenocarcinoma (PAAD) is still unclear. The present study was designed to examine the expression profile of TXLNA and explore its prognostic significance in PAAD patients and the possible molecular regulatory mechanism by analyzing a series of data from databases, including GEPIA, LOGpc, STRING, and GeneMANIA. The results indicate that TXLNA mRNA and protein were remarkably increased in PAAD tissues compared with normal pancreatic tissues. The high TXLNA expression was significantly correlated with superior overall survival (OS), disease-free interval (DFI), disease specific survival (DSS), and progression-free interval (PFI) for PAAD patients. In summary, high TXLNA expression could predict favourable OS, DFI, DSS, and PFI for PAAD patients, and it might be as potential prognostic biomarkers and targets for PAAD.

show abstract

Conditionally induced RAGE expression by proximal airway epithelial cells in transgenic mice causes lung inflammation

Cited by 12 publications

References 43 publications

Acute pulmonary effects of aerosolized nicotine

Acute pulmonary effects of aerosolized nicotine

Blockade of RAGE ameliorates elastase‐induced emphysema development and progression via RAGE‐DAMP signaling

High TXLNA Expression Predicts Favourable Outcome for Pancreatic Adenocarcinoma Patients

Contact Info

Product

Resources

About