What to Blame for That Sunburn (Aside From Yourself)

June 10, 2012 § Leave a comment

Photo by Lykaestria/Wikicommons

This is the sort of weather in which I can easily burn within the space of 30 to 45 minutes. That’s assuming I’m fool enough to stand outside in midday with neither sunscreen nor embarrassingly floppy hat. I do actually try to avoid that sort of behavior, but it can happen.

Within the first few hours of such exposure, my skin cells—keratinocytes—will begin churning out everything from inflammatory chemicals to immunosuppressants to nitric oxide, leaving me at once in pain, vulnerable to infection, and hot to the touch. White blood cells and prostaglandins will course through the area, adding to the mess. Worse yet, in some of my skin cells, the UV radiation will physically wrench apart and badly rebind key segments of my DNA, leaving misshapen bulges in its wake—like a long piece of string pinched in spots into tiny, doubled-up loops. My genetic copyediting team might be able to salvage some of these cells but others, past the point of no return, will push their self-destruct button and initiate suicide.

For the next few days, I will spend too much time taking cool showers and feeling sorry for myself.

But there’s one piece to this chain of events that’s missing: how did my skin know in the first place to do all this? What’s the molecular tripwire here?

Enter a new study from a crew of researchers out of San Diego, Miami, and New Jersey. With that question in mind, they performed an elegant series of experiments in both mice and skin cells in a dish. Their answer: it comes down to RNA. Specifically, sun-damaged RNA that tips off a molecular pattern-recognizer, which jumpstarts the inflammatory pathways, which snowballs into a miserable, sunburned chemical party on my skin.

Working backwards, here’s how they found it. The researchers first nailed down whether UV-exposed skin cells were, in and of themselves, enough to trigger inflammation. They added burned cells to a dish of unburned cells, and wouldn’t you know it: inflammatory chemicals poured out, particularly one called tumor necrosis factor-alpha, or TNF-α. TNF-α’s a big shot in sunburns and a known player in everything from cell death to inflammation to immune suppression, so the team zeroed in on that. Curiously, they noticed, those burned cells also caused the release of something called TLR-3—a pattern recognizer that specializes in detecting strands of double-stranded RNA. When they knocked out the TLR3 gene in the cells (and in mice), and they stopped the TNF-α.

But what’s causing the TLR3 to come out? To answer that, the crew ran through all the RNA being produced in a sunburned cell, compared to an unburned counterpart, and found a glaring discrepancy: burned cells create a broken, twisted version of an RNA typically found in a cell’s nucleus. And the damage was just the type to attract the pattern recognizer TLR3.

Straight-up, this type of RNA won’t kick off inflammation in a mouse’s skin—but if you expose the RNA to UV light and then apply it, it does. But get rid of the mouse’s TLR3 gene and that mutant RNA does him no harm. No inflammation, no burn. So the theory goes, a burn’s effects happen like this: Sunlight >> Damaged RNA >> TLR3 >> TNF-α and general inflammation.

As the authors point out, sunlight is already known to directly, physically damage genetic materials. For one thing, there’re its effects on DNA I mention earlier on, which can lead to skin cancer. Past studies have shown that sunlight can also do essentially the same thing to RNA; in this study, that mechanism appears to be a big part of what even makes a sunburn happen. And while we might curse that broken RNA and the pattern recognizer that finds it, it may be this sequence of events is doing us a favor. “We could speculate that the release of these inflammatory cytokines helps to sort of clean up the environment and stimulate wound healing. It may reduce cells that have mutated, or clear the necrotic debris,” says Richard Gallo, one of the study’s authors. “There’s likely to be a lot of beneficial effects of this that we may be able to study.” It also provides a new pathway to examine for phototherapy researchers as they fine-tune and improve the safety of such treatments.

For the rest of us though, no excuses: wear your damn sunscreen.

Bernard JJ, Cowing-Zitron C, Nakatsuji T, et al. Ultraviolet radiation damages self noncoding RNA and is detected by TLR3. Nature Medicine advance online publication, 08 July 2012. (doi: 10.1038/nm.2861)

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