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Lipid that Aids Normal Skin Turnover May Help Psoriasis

A lipid that helps keep skin cell turnover on track may help restore healthy turnover in psoriasis, investigators say.

Topical application of the lipid phosphatidylglycerol, or PG, on a mouse model of psoriasis reduced inflammation as well as characteristic, raised skin lesions, they report in the Journal of Investigative Dermatology.

They had already shown that PG has a role in both regulating the function of the major cell type in our skin called keratinocytes and suppressing skin inflammation.

Now they have the first evidence that PG inhibits toll-like receptor activation by the antimicrobial peptides produced by those skin cells, says Dr. Wendy B. Bollag, cell physiologist in the Department of Physiology at the Medical College of Georgia at Augusta University.

Toll-like receptors are a family of receptors that detect external invaders as well as internal damage signals then activate an immune response. Our skin is our largest organ and front line of defense, and a variety of skin cell types make antimicrobial peptides, which function like an endogenous antibiotic to help the skin protect us.

The common skin condition psoriasis upsets the works by increasing both the production of skin cells and production of these antimicrobials by those cells.

In some patients it may be a problematic immune system that initiates the vicious cycle of skin cells producing proteins called cytokines that call in more immune cells that make more cytokines that cause skin cells to make even more cytokines and excessively proliferate, says Bollag. In others, the antimicrobials may initiate the vicious cycle.

Either way, more antimicrobials get produced which is probably beneficial since psoriasis also impairs the skin’s ability to prevent invaders.

But these high levels of antimicrobials also produce an inflammatory response much like an invader’s might, resulting in the red, flaky patches that typically surface on high-touch areas like the elbows, forearms and knees and also show up on the scalp and elsewhere, says Bollag, the study’s corresponding author.

Because at higher levels, the body sees these protective antimicrobial peptides as danger-associated molecular patterns, or DAMPS, which, as the name indicates, it views as signs of danger. DAMPS then activate toll-like receptors.

It’s the increased and chronic level in psoriasis that heightens the awareness and response, says first author Dr. Vivek Choudhary, molecular biologist and physiologist in the MCG Department of Physiology.

Once toll-like receptors get activated, the immune system makes proinflammatory cytokines that bring in T cells, which help drive the immune system attacks.

“It’s actually T cells that help maintain the disease,” Bollag says, “But we are thinking that the innate immune system is sort of what initiates it,” she says of that toll-like receptor activation.

 

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Source: EurekAlert!