New Insights Into the Role of Thiocyanate in Cystic Fibrosis Revealed in Study

New Insights Into the Role of Thiocyanate in Cystic Fibrosis Revealed in Study

Researchers at the University of Pennsylvania recently revealed new insights into the development of cystic fibrosis (CF) and other disorders linked to inflammation based on the role played by the thiocyanate ion. The study was published in the journal PNAS and is entitled “The antioxidant role of thiocyanate in the pathogenesis of cystic fibrosis and other inflammation-related diseases.

CF is a rare, life-threatening genetic disease in which a defective gene called the cystic fibrosis transmembrane conductance regulator (CFTR) induces a salt imbalance, causing the body to form unusually thick, sticky mucus that can obstruct the airways and promote dangerous lung infections resulting in exaggerated inflammation and serious respiratory and gastrointestinal manifestations. The majority of the CF patients die due to respiratory failure. It is estimated that almost 75,000 individuals worldwide suffer from CF, including 30,000 in the United States.

CFTR is an ion channel. Ion channels form protein membranes on the surface of cells that are responsible for controlling the flow of electrical signals, which are crucial for cell life. The CFTR ion channel conducts chloride (Cl−) and thiocyanate (SCN−) ions across cells’  epithelial cell membranes, which when working correctly helps cells avoid the accumulation of harmful hydrogen peroxide (H2O2) and hypochlorite (OCl−) in human tissues.

The way that CFTR achieves this is through the production of a protein called lactoperoxidase (LPO), which is present in both the respiratory and digestive systems. LPO is able to transform SCN− into hypothiocyanite (OSCN−), which is an antimicrobial compound that is harmless to human tissues, and even helps to consume the dangerous H2O2. Another important protein involved in this process is myeloperoxidase (MPO; released by white blood cells), which in healthy patients oxidizes Cl− and SCN− into compounds that are safe for the body.

In the study, the research team hypothesized that because CFTR mutations are related to the absence of adequate SCN− levels in CF patients, there is an overproduction of the harmful OCl− compound, which results in the severe lung injuries associated with the disease.

Using a human lung epithelial cell line, researchers found that the dysfunctional myeloperoxidase process in CF indeed causes severe cell injury and death through the production of OCl−. Conversely, the team reported that when SCN− is present in appropriate levels, it is capable of preventing damage to lung cells, and also protects cells against the potentially dangerous H2O2.

When tested in three other mouse and human cell lines (arterial cells, neuronal cells and pancreatic cells) that are relevant for inflammation-related disorders, SCN− at concentrations of 100 μM or higher was able to strongly mitigate the cytotoxicity of MPO.

Humans can obtain the natural antioxidant SCN− from edible plants, and the ion levels in the general population ranges from 10 to 140 μM.

Based on these new insights, the research team proposes that insufficient levels of SCN− found in cystic fibrosis patients impair the protection provided to cells against these harmful compounds accumulating in human tissues, which results in an increase in inflammation and worse clinical outcomes in inflammatory diseases like CF. With this in mind, future CF therapies might be able to address insufficient SCN− levels, improving symptoms and quality of life associated with CF.

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