Vaping-Dependent Pulmonary Inflammation Is Ca2+ Mediated and Potentially Sex Specific.

Here we use the SCIREQ InExpose system to simulate a biologically relevant vaping model in mice to investigate the role of calcium signaling in vape-dependent pulmonary disease as well as to investigate if there is a gender-based difference of disease. Male and female mice were vaped with JUUL Menthol (3% nicotine) using the SCIREQ InExpose system for 2 weeks. Additionally, 2-APB, a known calcium signaling inhibitor, was administered as a prophylactic for lung disease and damage caused by vaping. After 2 weeks, mice were exposed to lipopolysaccharide (LPS) to mimic a bacterial infection. Post-infection (24 h), mice were sacrificed, and bronchoalveolar lavage fluid (BALF) and lungs were taken. Vaping primed the lungs for worsened disease burden after microbial challenge (LPS) for both males and females, though females presented increased neutrophilia and inflammatory cytokines post-vape compared to males, which was assessed by flow cytometry, and cytokine and histopathological analysis. This increased inflammatory burden was controlled by calcium signaling inhibition, suggesting that calcium dysregulation may play a role in lung injury caused by vaping in a gender-dependent manner.

An assessment of vaping-induced inflammation and toxicity: A feasibility study using a 2-stage zebrafish and mouse platform.

It is currently understood that tobacco smoking is a major cause of pulmonary disease due to pulmonary/lung inflammation. However, due to a highly dynamic market place and an abundance of diverse products, less is known about the effects of e-cigarette (E-cig) use on the lung. In addition, varieties of E-cig liquids (e-liquids), which deliver nicotine and numerous flavor chemicals into the lungs, now number in the 1000s. Thus, a critical need exists for safety evaluations of these E-cig products. Herein, we employed a "2-stage in vivo screening platform" (zebrafish to mouse) to assess the safety profiles of e-liquids. Using the zebrafish, we collected embryo survival data after e-liquid exposure as well as neutrophil migration data, a key hallmark for a pro-inflammatory response. Our data indicate that certain e-liquids induce an inflammatory response in our zebrafish model and that e-liquid exposure alone results in pro-inflammatory lung responses in our C57BL/6J model, data collected from lung staining and ELISA analysis, respectively, in the mouse. Thus, our platform can be used as an initial assessment to ascertain the safety profiles of e-liquid using acute inflammatory responses (zebrafish, Stage 1) as our initial metric followed by chronic studies (C57BL/6J, Stage 2).

Calcium-Dependent Pulmonary Inflammation and Pharmacological Interventions and Mediators.

Pulmonary diseases present a significant burden worldwide and lead to severe morbidity and mortality. Lung inflammation caused by interactions with either viruses, bacteria or fungi is a prominent characteristic of many pulmonary diseases. Tobacco smoke and E-cig use ("vaping") are considered major risk factors in the development of pulmonary disease as well as worsening disease prognosis. However, at present, relatively little is known about the mechanistic actions by which smoking and vaping may worsen the disease. One theory suggests that long-term vaping leads to Ca2+ signaling dysregulation. Ca2+ is an important secondary messenger in signal transduction. Cellular Ca2+ concentrations are mediated by a complex series of pumps, channels, transporters and exchangers that are responsible for triggering various intracellular processes such as cell death, proliferation and secretion. In this review, we provide a detailed understating of the complex series of components that mediate Ca2+ signaling and how their dysfunction may result in pulmonary disease. Furthermore, we summarize the recent literature investigating the negative effects of smoking and vaping on pulmonary disease, cell toxicity and Ca2+ signaling. Finally, we summarize Ca2+-mediated pharmacological interventions that could potentially lead to novel treatments for pulmonary diseases.