Itchy responses on the role of lipids in psoriasis


While we often stress the importance of the heart and brain, human skin is the largest organ in the body and is vital for our survival. It serves as a water barrier, protecting the body from dehydration, extreme temperatures, and harmful chemicals. Lipids in the skin are essential for its water barrier function, because fat and water do not mix.

Christopher Thomas is a lecturer and researcher at the School of Pharmacy and Pharmaceutical Sciences at Cardiff University whose research focuses largely on oxidized lipids and their role in human health and disease, particularly in the skin. Thomas became interested in skin while pursuing a doctorate. in chemistry and working on the development of topical treatments for rheumatoid arthritis.

“We were trying to get fatty acids and fish oils through the skin,” Thomas said.

More important research questions have arisen for Thomas regarding the physiology of the skin and how products are metabolized once they enter the skin. His postdoctoral studies then focused on lipoxygenase, or LOX, enzymes within platelets in the blood. Thomas’ current research is a marriage of his earlier work; he is now studying the role of LOX enzymes in the skin.

In a recent article by Lipid Research Journal, Thomas et al. Describe the study of a biosynthetic pathway in the skin that is vital for the formation of the complex skin barrier in mammals. In this way, ceramide lipids containing a fatty acid, linoleic acid, are oxidized by LOX enzymes. Ceramides of different carbon lengths are oxygenated by LOX. After a few intermediate steps, a final hydrolysis step gives an end product called 9,10,13-trihydroxy-10E-octadecenoic acid, which has been found at higher than normal levels in patients with eczema.

Researchers have little knowledge of the exact location in the skin layers of these intermediate and terminal species and their roles in health and disease. Thomas developed methods to study the amount and location of these species, using liquid chromatography with tandem mass spectrometry. Developing methods for any type of lipid system can be quite difficult, he said, as lipids are repelled by all solutions containing water.

As part of this research, the team analyzed samples of human psoriatic skin and showed that the linoleic acid oxygenation pathway was severely deregulated. Non-oxidized intermediates in the pathway were significantly elevated compared to non-psoriatic skin samples, and oxygen species were reduced.

The researchers also used a publicly available data set from the Gene Expression Omnibus to compare the genetic profile of psoriatic lesion skin to that of unaffected skin in patients with psoriasis. They found that genes for the entire oxygen species biosynthesis pathway described here are more expressed in the skin of human psoriatic lesions. This suggests that the regulatory machinery to control even unaffected skin lipid metabolism is abnormal in patients with psoriasis.

Thomas’ next lines of research will use an exciting new addition to the lab: a 3D printer to generate new skin models. This is a project shared with several other Cardiff researchers who are interested in studying printed skin from various research angles.

“It’s a collaborative feeling where we’re all interested, but we all have our hats slightly different,” he said.

Thomas added that he also sees 3D printed skin as a way to further the goal of producing representative healthy and diseased human skin models, which could help reduce animal testing in the pharmaceutical and pharmaceutical industries. cosmetic.

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