A commonly prescribed class of drugs, glucocorticoids, are used for their anti-inflammatory effects. They have side effects that are not well understood, however, and users can build resistance to these drugs. A new study has provided insight into what is causing the side effects that are sometimes observed in patients, and could also help explain how resistance develops. The work, by scientists at the University of Cambridge, has been published in Cell Reports.
Glucocorticoids are hormones that are naturally produced by the body, functioning to aid in stress regulation. This work adds to our understanding of how glucocorticoid drugs can improve the symptoms of many different diseases, like eczema, asthma, and even some types of cancers. As prescriptions, glucocorticoids are considered to be generally safe and well-tolerated and are widely used. But their efficacy is limited by the side effects that some people experience.
For this work, the researchers used powerful microscopy to assess the three-dimensional structure of DNA in mouse immune cells that had been exposed to glucocorticoid drugs. They observed dynamic shifts in the organization and form of the genetic material in the cells, after only five minutes of treatment with the drug. These effects remained even five days after that application.
"Glucocorticoids are important in health and disease and we are struck by the magnitude and persistence of the changes we have found. The results provide a really exciting direction for further work to understand how the DNA structure is controlled and how it can be measured in a clinical context,” said study co-leader Alastair Jubb, Clinical Lecturer in Anaesthesia and Intensive Care Medicine at the University of Cambridge."
The physical structure of DNA, how it is folded, is important to the function of cells. Since glucocorticoids are present in our bodies and have a role in the stress response, this study could help us understand how trauma can have long-term impacts on the body.
"These exciting results are a step change in how we understand the effect of glucocorticoids, which are safe drugs but have side effects in some people,” said co-study leader Wendy Bickmore, Director of the MRC Human Genetics Unit at the University of Edinburgh. The investigators plan to continue their work on this project. “Our next steps are to analyze whether these same changes can be detected in cells from patients who are taking glucocorticoids."
Learn more about glucocorticoids from the video.