PM2.5 particulate matter lowers the levels of a protein, sirtuin 2, which regulates important physiological processes underlying theinflammation of the airways. This is revealed by a study that also identifies a potential therapeutic avenue

What this article is about

• A mechanism has been discovered through which PM2.5 fine particulate matter promotes airway inflammation
• It has been observed that PM2.5 reduces sirtuin 2 levels and that it is precisely this mechanism that triggers the inflammatory process
• In mice, a compound called triptolide has been shown to be able to inhibit inflammation

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Italy ranks first in Europe for the number of deaths due to fine particulate matter, according to data from a recent study in The Lancet, and eleventh for deaths from PM2.5 fine particulate matter. PM2.5 damages the lungs and other organs and tissues, increasing the risk of respiratory infections, various types of cancer, heart disease and more. Now, a study conducted by the Air Force Medical University, a Chinese military institution dedicated to academic training, has identified a possible mechanism through which PM2.5 particulate matter would trigger inflammation in the airways. Understanding the origins of this process is important for identifying new preventive strategies and possible therapeutic targets. The key would lie in sirtuinsSirtuins are proteins expressed by SIRT genes that perform an enzymatic activity, which means they stimulate chemical reactions essential for the body. Their function has been ascertained by several studies, although there still seems to be a lot to know about them. SIRTs in short:
• are proteins with enzymatic properties
• regulate the metabolic processes related to insulin resistance
• have a control over immunity
• have a fundamental role in epigenetics
• are involved in defences against cancer
, a group of 7 proteins that are very important for our body, and in particular in one of them, sirtuin 2 (SIRT2). The results, so far obtained in an animal model, are published in the journal Frontiers in Medicine.

PM2.5 fine particulate matter

PM2.5 particulate matter is made up of particles with a size equal to or smaller than 2.5 micrometers (thousandths of a millimeter). These very fine particles can enter the bronchi. Moreover, unlike coarser particulate matter, such as PM10, they can also reach the pulmonary alveoli and from there pass into the blood.

The scientists showed that PM2.5 is able to cause airway inflammation and bronchial hyperreactivity in mice. The research identified a possible gear behind the “machine” of inflammation. The mechanism is complex and consists of several steps.

A complex gear

Sirtuins also play a role in these steps: proteins naturally produced by our body that regulate important metabolic processes and that exert an “anti-aging” action on cells, helping to prevent numerous diseases. We already knew that sirtuin 2 acts as a mediator within a physiological process at the root of inflammation. More specifically, SIRT2 modulates certain chemical reactions involving another protein, abbreviated p65, which in turn underlies the activation of the protein complex NF-κB. The latter plays an essential part in inflammation and in innate immunity, the first line of defense we have from birth, and also plays a role in the development and progression of cancer. The NF-κB protein is activated in all the reactions of cells stimulated by external stimuli, including attacks by viruses, bacteria and other pathogens.

How PM2.5 acts

In the study, the scientists found that exposure to PM2.5 fine particulate matter reduces sirtuin 2 (SIRT2) levels in bronchial tissues. This drop activated specific chemical reactions of the p65 protein that triggered the physiological pathway at the origin of airway inflammation. In the study, the inflammation subsequently promoted excessive bronchial reactivity and a thickening of certain parts of the tissue in the mice. In addition, mucus secretion was greater and the researchers observed a narrowing of the trachea. In animals in which SIRT2 had been silenced in the laboratory, the inflammation and deterioration were more marked.

There is some good news: the researchers found that triptolide, a compound known as an inhibitor of the p65 protein, intervenes in the inflammatory process and manages to put a significant brake on it. The results are still preliminary, but they shed light on a previously unknown mechanism through which fine particulate matter could damage our airways.