Modelling Respiratory Damage Caused by Air Pollution
Smooth Muscle & Skeletal Muscle Satellite Cells
The lungs are the largest organ in the body primarily responsible for respiration, the exchange of oxygen and carbon dioxide that is essential to proper cellular function. The large surface area of the lung tissue makes it susceptible to pollutants in the air that can negatively affect the health of airway cells. Bronchial smooth muscle cells are critical to maintaining airway structure and normal function of the lungs; their abundance in the lung tissue means they are likely to be among the first cells to come into contact with air pollutants in the human body, which makes them excellent models for studying the effects on air pollution on the lungs.
Smooth muscle cells along with cardiac, skeletal, and skeletal satellite cells make up the body’s muscle system responsible for a diverse array of functions in the body including locomotion, cardiac function, and disease, blood pressure regulation, airway inflammation, wound repair, and more.
Interested in muscle cells for your research? Lifeline® offers a variety of smooth muscle cells (SMCs) from different tissue types as well as skeletal muscle satellite cells. Check out our catalog for more information:
- Prostate SMCs
- Bronchial/Tracheal SMCs
- Lung SMCs
- Aortic SMCs
- Bladder SMCs
- Coronary artery SMCs
- Pulmonary artery SMCs
- Uterine SMCs
- Primary Human Skeletal Muscle Satellite Cells
Research Using Bronchial/Tracheal Smooth Muscle Cells
The World Health Organization has recognized that small particulate matter (PM10 and PM2.5; smaller than 10 and 2.5 μm respectively) in air pollution threatens global public health, leading to respiratory and dermatological conditions but how these particles attack the cells is not fully understood. Intracellular calcium ([Ca2+]i) is a universal second messenger within cells and increases in cytosolic Ca2+ concentration is an indicator of environmental stress. In a recent publication, Choi and Colleagues selected Lifeline’s Human Bronchial/Tracheal Smooth Muscle (HBT-SM) cells as a primary reporter for Ca2+ signaling and keratinocytes for their studies since the cells of the respiratory tract and skin are directly affected by primary contact with air pollution. The authors developed a custom perfusion-based system to model the transient intracellular calcium changes caused by exposure to air pollution in the form of diesel particle matter (DPM, 2.5PM). This model was then used to find potential candidates that could protect against cytosolic Ca2+ changes caused by air pollution.
Exposure to DPM was found to induce increases in [Ca2+]i in both HBT-SMs and keratinocytes in a concentration-dependent manner using the perfusion platform. In testing compounds that could mitigate the effect of DPM on the cells, Phellodendron amurense bark extract (PAE), a traditional medicine, was found to inhibit Ca2+ influx caused by air pollution exposure. This promising result prompted the authors to look further into the molecular mechanism responsible for the Ca2+ influx and the involvement of PAE. the authors looked at PAR-2 because previous studies with human bronchial epithelia show that PAR-2 activation by matrix metalloproteinase-1 (MMP-1) activates TRPV4 channels leading to Ca2+ influx, similar to the results observed here. Competitive assays with PAR-2 agonists demonstrated that PAR-2 activation caused by DPM exposure promotes Ca2+ influx. Conversely, treatment with PAR-2 antagonists produced similar outcomes as PAE treatment indicating a direct inhibition mechanism of PAR-2 activation. In depth transcriptional analyses confirmed upregulation of proinflammatory cytokine genes, IL-8, IL-6, and TNF-α. Additionally, tight-junction components ZO-1 and Occludin were downregulated in the keratinocytes suggesting PAR-2 activation leads to skin barrier dysregulation or loss of skin integrity, which could cause the severe skin conditions observed with prolonged exposure to air pollution.
To further understand the protective role of PAE, Choi and Colleagues used peptide fractionation and NMR spectroscopy to identify 4-O-feruloylquinic acid (FQA) and the other two known active compounds most responsible for its efficacy. FQA demonstrated the same effects on Ca2+ influx and PAR-2 regulation in the established perfusion model.
With its long history of herbal remedies in East Asia, products containing PAE could provide protection against air pollution. More research on the stability of FQA and the safety of PAE use will be helpful to further examine potential industrial applications.
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