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GEN News Highlights : Aug 19, 2009

Regulation of Antimicrobial Peptide by Vitamin D Found to Have Been Conserved for 60M Years

Findings help explain how overall immune response to a pathogen is maximized, as reported in BMC Genomics.

A new study has concluded that one part of the immune system, the ability of vitamin D to regulate antibactericidal peptides like cathelicidin, is so important that it is has been conserved through almost 60 million years of evolution and is shared only by primates. The cathelicidin peptide has several different biological activities in addition to killing pathogens, and it is not yet clear which one or combination of them makes vitamin D so essential to its regulation.

Researchers from Oregon State University (OSU) and the Cedars-Sinai Medical Center describe the presence of a genetic element that is specific to primates and involved in the innate immune response in a paper published in BMC Genomics. The genetic material called an Alu short interspersed element is part of what used to be thought of as junk DNA but is believed to have important roles in regulating and turning on the expression of other genes.

It has been known that in primates this action of turning on an optimal response to microbial attack only works properly in the presence of adequate vitamin D. Additionally, researchers understand that vitamin D prevents the adaptive immune response from overreacting and reduces inflammation.

In the current study the scientists specifically discovered that Alu allows vitamin D to boost the innate immune response by turning on cathelicidin. The scientists thus suggest that the overall effect of this action is likely to help prevent the immune system from overreacting.

“It's essential that we have both an innate immune response that provides an immediate and front line of defense, but we also have protection against an overreaction by the immune system, which is what you see in sepsis and some autoimmune or degenerative diseases,” explains Adrian Gombart, Ph.D., an associate professor of biochemistry and a principal investigator with the Linus Pauling Institute at OSU. “This is a very delicate balancing act, and without sufficient levels of vitamin D you may not have an optimal response with either aspect of the immune system.

“The antimicrobial peptide that we're studying seems to be involved not just in killing bacteria, but has other biological roles,” Dr. Gombart continues. “It recruits other immune cells and sort of sounds the alarm that something is wrong. It helps promote development of blood vessels, cell growth, and healing of wounds. And it seems to have important roles in barrier tissues such as skin and the digestive system. Vitamin D is very important for the health of the skin and digestive system, and putting the cathelicidin antimicrobial peptide gene under its regulation may be important in this function.”

Any one or some combination of those biological roles may be why vitamin D-mediated regulation of the antimicrobial peptide has been conserved in every primate species ever examined for its presence, researchers say, and did not disappear long ago through evolutionary variation and mutation. The evolution of primates into many different families and hundreds of species has been carefully tracked through genetic, molecular sequence, and fossil studies, but the presence of this regulatory element in primates is still largely the same as it's been for more than 50 million years.

The evolutionary survival of this genetic element and the placement of the cathelicidin antimicrobial peptide gene under the regulation of the vitamin D pathway “may enable suppression of inflammation while potentiating innate immunity, thus maximizing the overall immune response to a pathogen and minimizing damage to the host,” according to the scientists.