Iron and cell death affect intestinal inflammation

One of the mysteries is the role of reactive oxygen species (called reactive oxygen species, or ROS). These molecules are a normal metabolic product, but if there are too many of them, they begin to harm cells. So far, attempts to treat intestinal inflammation with antioxidants that neutralize ROS have not brought the expected success in humans.

The team led by Professor Yatrik Shah decided to look at the problem in a different way. They created a model of chronic intestinal inflammation in mice and studied which types of ROS are associated with the disease. It turned out that not everyone is dangerous, but a special type of molecules associated with fats – they damage the cells of the intestinal mucosa.

These lipid ROS trigger a unique cell death process called ferroptosis, which is iron-dependent. This is a new type of cell death for science, in which cells literally “burn up” from the inside. Moreover, scientists have discovered that the ACSL4 gene is active in inflamed intestinal tissues, which enhances this process.

Experiments on mice have confirmed that ACSL4 is particularly active in intestinal connective tissue cells and promotes the accumulation of harmful molecules, which leads to tissue destruction and exacerbation of inflammation.

Interestingly, this effect did not appear in healthy animals, which suggests that ferroptosis plays a key role in the context of the disease.

The discovery of this connection is very important, because now you can not just try to bring down the entire ROS level, but purposefully block ferroptosis. In experiments on mice, it has already been shown that drugs that suppress this process help alleviate symptoms.