Research sheds light on inflammatory mechanism of sunburn

Key Points

National report - Ultraviolet B (UVB) radiation damage to noncoding RNAs in keratinocytes initiates a cascade of events leading to the release of tumor necrosis factor-alpha (TNF-alpha), a cytokine central to the inflammatory skin response commonly known as sunburn.

The surprising discovery of this mechanism, which was published in Nature Medicine in July, has potential implications for better understanding of prevention, carcinogenesis and phototherapy, researchers say.

Lab details

Much of the work was done by post doctoral researcher Jamie J. Bernard in the lab of Richard L. Gallo, M.D., Ph.D., professor of medicine and chief of dermatology, University of California, San Diego.

Digging deeper, they determined that the lysates also increased expression of toll-like receptor 3 (TLR3). Knocking down that expression significantly reduced production of TNF-alpha and IL-6. It established the mechanism for regulating inflammation.

But what in the lysates was setting off the series of events?

The structure of the U1 loop domain of noncoding RNA looked like it could be a potential ligand for TLR3. And irradiation significantly increased the frequency of the molecule. A series of experiments confirmed that the irradiated, but not the nonirradiated, U1 molecule increased production of inflammatory cytokines.

Additional work suggests that U1 RNA must be taken up by keratinocytes and delivered to the endosome in order to activate TLR3 signaling, Dr. Gallo says.

"What is unique about the non-coding RNAs is that some of them have structures, such as the one we found, that are double-stranded, whereas most of the messenger RNAs are single-stranded," he says.

"Ultraviolet radiation damages RNA; in particular it breaks up these noncoding RNAs, and some of them when they are fragmented into little double-stranded pieces turn on an inflammatory reaction through the same pathway that we use to recognize viral RNAs," he explains. "This is the U1 RNA that we use as the prototype."

He readily acknowledges that there may be other processes contributing to the inflammation, but this appears to be a principle pathway.