The first warm rays of the sun in spring, the first sunbathing, the season’s first sunburn. It is hard to get a good night’s sleep on a lobster-red back, and the soothing cream sticks to the pyjamas. A recurring pattern of events that many people are familiar with from their own experience. However, up to now even scientists did not know what happens at a molecular level in the skin cells and how this causes the inflammation that leads to insomnia.

Skin cells contain inflammasome

ETH Zurich cell biologists in collaboration with the dermatology clinics of the University of Lausanne and Zurich University Hospital have now elucidated the mechanism underlying the inflammatory response of sunburn. The findings, which are in part astonishing, were published on Thursday 28 June 2007 in the on-line edition of the scientific journal “Current Biology”.(1) Thus the researchers were able to show for the first time that keratinocytes, the commonest cell type in the human epidermis, contain a protein complex that triggers an immune response. This is despite the fact that skin cells are not professional immune cells.

This protein complex, known as an inflammasome, initiates a whole chain reaction in the skin cells, ultimately culminating in the inflammation associated with sunburn. Assistant Professor Hans-Dietmar Beer, in whose work group at the Institute of Cell Biology (2) of ETH Zurich the paper originated, stresses that “The fact that keratinocytes contain a functioning inflammasome was in dispute in the literature up to now.” Moreover, the inflammasome is identical to that of phagocytes. The knowledge that this inflammasome can be activated by UVB radiation is also new. As a rule various pathogens – bacteria, viruses and the like – are required for activation in the case of phagocytes.

UVB radiation triggers a cascade

UVB radiation liberates an excess of calcium ions in the cell plasma of the keratinocytes. The inflammasome is not activated until this “overdose” is present. Exactly how this occurs is still unclear. However, the inflammasome brings the enzyme Caspase-1 into operation. This in turn generates the messenger substance Interleukin-1b (IL-1b) from a precursor, proIL-1b.

Sunburn on the upper arm: ETH Zurich researchers have uncovered the molecular processes in skin cells leading to this sort of unwanted and painful pattern (Photo: www.wikipedia.org) large

„Beer says “The inflammasome is essential for the activation of this messenger substance.” To survive, the cell must expel the Interleukin-1b and the constituents of the inflammasome as quickly as possible. Outside the cell these substances are ultimately responsible for propagating the inflammation – sunburn occurs.

Researching auto-immune diseases

Through their work, which was initially “only” a secondary project for the first author Laurence Feldmeyer, the researchers are laying a foundation for an improved understanding of UV-induced skin diseases, which also include some severe auto-immune diseases. Sabine Werner, ETH Zurich Professor of Cell Biology, says that many of these diseases are characterised by a permanently over-reacting inflammatory response. Therefore in the next phase the ETH Zurich researchers now plan to study keratinocytes from patients of this kind, to find out among other things whether these skin cells emit more Interleukin-1b than healthy ones. This might enable them to lay another cornerstone in the development of a medicine against inflammatory skin diseases.