Vitamin D Has Been Guiding Immunity for Millions of years

Byron's Comments:

Vitamin D is intimately linked to survival of humans against infectious disease.

Study Title:

Exaptation of an ancient Alu short interspersed element provides a highly conserved vitamin D-mediated innate immune response in humans and primates.

Study Abstract:

Background
About 45% of the human genome is comprised of mobile transposable elements or “junk DNA”. The exaptation or co-option of these elements to provide important cellular functions is hypothesized to have played a powerful force in evolution; however, proven examples are rare. An ancient primate-specific Alu short interspersed element (SINE) put the human CAMP gene under the regulation of the vitamin D pathway by providing a perfect vitamin D receptor binding element (VDRE) in its promoter. Subsequent studies demonstrated that the vitamin D-cathelicidin pathway may be a key component of a novel innate immune response of human to infection. The lack of evolutionary conservation in non-primate mammals suggested that this is a primate-specific adaptation. Evidence for evolutionary conservation of this regulation in additional primate lineages would provide strong evidence that the TLR2/1-vitamin D-cathelicidin pathway evolved as a biologically important immune response mechanism protecting human and non-human primates against infection.

Results
PCR-based amplification of the Alu SINE from human and non-human primate genomic DNA and subsequent sequence analysis, revealed perfect structural conservation of the VDRE in all primates examined. Reporter gene studies and induction of the endogenous CAMP gene in Rhesus macaque peripheral blood mononuclear cells demonstrated that the VDREs were conserved functionally. In addition, New World monkeys (NWMs) have maintained additional, functional steroid-hormone receptor binding sites in the AluSx SINE that confer retinoic acid responsiveness and provide potential thyroid hormone receptor binding sites. These sites were less well-conserved during human, ape and Old World monkey (OWM) evolution and the human CAMP gene does not respond to either retinoic acid or thyroid hormone.

Conclusion
We demonstrated that the VDRE in the CAMP gene originated from the exaptation of an AluSx SINE in the lineage leading to humans, apes, OWMs and NWMs and remained under purifying selection for the last 55–60 million years. We present convincing evidence of an evolutionarily fixed, Alu-mediated divergence in steroid hormone nuclear receptor gene regulation between humans/primates and other mammals. Evolutionary selection to place the primate CAMP gene under regulation of the vitamin D pathway potentiates the innate immune response and may counter the anti-inflammatory properties of vitamin D.

From press release:

A new study has concluded that one key part of the immune system, the ability of vitamin D to regulate anti-bactericidal proteins, is so important that is has been conserved through almost 60 million years of evolution and is shared only by primates, including humans – but no other known animal species.

The fact that this vitamin-D mediated immune response has been retained through millions of years of evolutionary selection, and is still found in species ranging from squirrel monkeys to baboons and humans, suggests that it must be critical to their survival, researchers say.

Even though the “cathelicidin antimicrobial peptide” has several different biological activities in addition to killing pathogens, it’s not clear which one, or combination of them, makes vitamin D so essential to its regulation.

The research also provides further evidence of the biological importance of adequate levels of vitamin D in humans and other primates, even as some studies and experts suggest that more than 50 percent of the children and adults in the U.S. are deficient in “the sunshine vitamin.”

“The existence and importance of this part of our immune response makes it clear that humans and other primates need to maintain sufficient levels of vitamin D,” said Adrian Gombart, an associate professor of biochemistry and a principal investigator with the Linus Pauling Institute at Oregon State University.

In a new study in the journal BMC Genomics, researchers from OSU and the Cedars-Sinai Medical Center describe the presence of a genetic element that’s specific to primates and involved in the innate immune response. They found it not only in humans and their more recent primate ancestors, such as chimpanzees, but also primates that split off on the evolutionary tree tens of millions of years ago, such as old world and new world primates.

The genetic material – called an Alu short interspersed element – is part of what used to be thought of as “junk DNA” and makes up more than 90 percent of the human genome. That genetic material, however, is now understood to often play important roles in regulating and “turning on” the expression of other genes.

In this case, the genetic element is believed to play a major role in the proper function of the “innate” immune system in primates – an ancient, first line of defense against bacteria, viruses and other pathogens, in which the body recognizes something that probably doesn’t belong there, even though the specific pathogen may never have been encountered before.

“Many people are familiar with the role of our adaptive immune system, which is what happens when we mount a defense against a new invader and then retain antibodies and immunity in the future,” Gombart said. “That’s what makes a vaccine work. But also very important is the innate immune system, the almost immediate reaction your body has, for instance, when you get a cut or a skin infection.”

In primates, this action of “turning on” an optimal response to microbial attack only works properly in the presence of adequate vitamin D, which is actually a type of hormone that circulates in the blood and signals to cells through a receptor. Vitamin D is produced in large amounts as a result of sun exposure, and is available in much smaller amounts from dietary sources.

Vitamin D prevents the “adaptive” immune response from over-reacting and reduces inflammation, and appears to suppress the immune response. However, the function of the new genetic element this research explored allows vitamin D to boost the innate immune response by turning on an antimicrobial protein. The overall effect may help to 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,” Gombart said. “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.”

After years of research, scientists are continuing to find new roles that vitamin D plays in the human body. It can regulate the actions of genes that are important to bone health, calcium uptake, and inhibition of cell growth. It helps regulate cell differentiation and, of course, immune function.

“The antimicrobial peptide that we’re studying seems to be involved not just in killing bacteria, but has other biological roles,” Gombart said. “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 said, 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,” the researchers wrote in their conclusion.

Vitamin D deficiency is an issue of growing concern among many scientists, due to changing lifestyle or cultural trends in which many people around the world get less sun exposure and often inadequate dietary levels of the vitamin. It’s a special problem with the elderly, which often have reduced exposure to sunlight and less ability to produce vitamin D in their skin – and at least partly as a result, are more susceptible to bone fractures, chronic inflammation and infectious disease.

Study Information:

Adrian F Gombart, Tsuyako Saito, H Phillip Koeffler Exaptation of an ancient Alu short interspersed element provides a highly conserved vitamin D-mediated innate immune response in humans and primates. BMC Genomics 2009 July 
Linus Pauling Institute, Department of Biochemistry and Biophysics, Oregon State University, Corvallis, Oregon, USA.

Full Study:

http://www.biomedcentral.com/1471-2164/10/321


Related Entries: Whiplash, Thyroid, and Adrenals
Brain Inflammation Now Documented in Chronic Fatigue Syndrome
Brain Protective Effects of Proathocyanidins
Nutrient Highlight: Discover the Best Form of Folate
Lutein and Zeaxanthin Offset Gene Weaknesses that Cause Macular Degeneration
Lycopene Builds Its Anti-Prostate Cancer Case
Carotenes Improve the Quality of Semen
Vitamin B12 as Methylcobalamin Repairs Nerves & Lowers Pain
Folic Acid Activates Neural Stem Cells for Brain Rejuvenation
Chromium Improves Insulin Function & Reduces Binge Eating
How Fiber and Niacin Protect Against Colon Inflammation and Cancer
Berries Have Anti-Aging Impact on Immune System
Strawberries Reduce Cardiovascular Risk
Friendly Flora Improves Fatty Liver Disease
Flavonoid Intake Improves Cardio Health in At-Risk Men
Polyphenols and Essential Fatty Acids Reduce Cardio Risk in Overweight People
Vitamin C Reduces the Risk for Hemorrhagic Stroke
Testosterone Therapy Increases Heart Attack Risk
Magnesium Intake Linked to Lower Cardiovascular Inflammation
Q10 Boosts Energy, Nerves, Muscles & Metabolism
Coenzyme Q10 Remarkably Improves Circulation
Tyrosine Helps Maintain Mental Ability Under Stress
Green Tea Extract Lowers Blood Pressure, Cholesterol, Blood Sugar & Inflammation
Poor Flexibility is a Sign of Stiff Arteries
A Sluggish Lymph System Causes Snoring & Sleep Apnea
DHA is Vital to Cardiovascular Wellness
Magnesium Supplements Lower Blood Pressure, Prevent Calcification
Magnesium for the Prevention of Heart Disease
Pomegranate Protects HDL Cholesterol from Damage
Pomegranate Blocks Flu Replication
Tocotrienols:  Twenty Years of Dazzling Cardiovascular and Cancer Research
Is Resveratrol the Fountain of Youth?
Grape Seed Extract Lowers Blood Pressure
Scientists Tout Resveratrol as a Primary Nutrient for Cardio Health
Leptin, Thyroid, and Weight Loss
Excess Appetite Causes Abdominal Fat
Low Energy? Detect Thyroid Related Fatigue
Curcumin Boosts AMPK Activation, Prevents Fatty Liver
Quercetin Activates Mitochondrial Biogenesis
Quercetin Guards Against Inflammation-Induced Bone Loss
Head Injuries Double or Triple the Risk of Early Death
Fatty Fish Consumption Lowers the Risk of Type 2 Diabetes by 33%
Flavonoids Continue to Show Potent Diabetes Prevention
Vitamin K2 Decreases Bone Loss in Postmenopausal Women
Cissus Quadrangularis Enhances Fracture Healing
Cissus Quadrangularis Reduces Exercise-Related Joint Pain
Nobiletin and Tangeretin Help Protect Against Bone Loss
Nobiletin and Tangeretin Inhibit Respiratory Virus
Oregano Oil Inhibits Biofilm Formation
Bromelain Helps Chronic Sinus Inflammation
Curcumin Demonstrates Potent Anti-Flu Properties
Quercetin Protects Brain and Body from Low Oxygen Stress
Ubiquinol Q10 Protects Against Magnified Tissue Injury
Ubiquinol Q10 Protects Eyes of Diabetic Patients
Limonene Promotes Healing of Digestive Lining
Magnesium Intake Reduces Mortality
Fiber is Vital for Cardio Health
Friendly Flora Boosts Weight Loss in Obese Women
Tocotrienols Help Correct Fatty Liver in Humans
Vitamin E Boosts Quality of Life for Alzheimer’s Patients
Astaxanthin Demonstrates Brain Protection & Rejuvenation
Top 10 Health Stories of 2013
Resveratrol’s Amazing Anti-Aging Effect on Circulation
Grape Seed Extract Normalizes Blood Pressure in Mild Hypertension Patients
Don’t Let Bacterial Infections Set Up Shop
Viral Replication Fueled by Sugar
Anti-Vitamin Propaganda Hits a Fever Pitch
Antacid Medications Cause Vitamin B12 Deficiency, Speed Aging
Men Should Take Folic Acid Prior to Conception to Prevent Birth Defects
Exercise Potently Reduces the Risk for Diseases of Aging
Fisetin Demonstrates Potent Bone Protection Properties
Green Tea (EGCG) Improves Body Weight and Autoimmune Arthritis
Low Midlife Iron Contributes to Declining Cognitive Function in Women
DHA Reduces Inflammation in Brains of Alzheimer’s Patients
Low Magnesium Linked to Poor Vitamin D Status
Vitamin D Lowers Depression and Nerve Pain in Women with Type 2 Diabetes
Adequate Vitamin D is Needed to Prevent Brain Damage
Nutrition Makes Anti-Aging Possible: Secrets of Your Telomeres
Acetyl-L-Carnitine and Lipoic Acid Rejuvenate Stressed Mitochondria
Low DHA and EPA Linked to Major Depression and Anxiety
Higher Dose DHA and EPA Reduce Infection Toxins
DHA and EPA Help People with Dry Eye Syndrome
Tocotrienol E Supports Bone Health
Antioxidants and Magnesium Linked to Better Hearing
Bovine Lactoferrin Anti-Flu Properties
Olive Leaf Extract Improves Blood Sugar Metabolism
Bovine Colostrum’s Potent Immune-Support Activity
EPA and DHA Boost Mental Health Scores in Healthy Adults
DHA and EPA Boost Brain Function in Children with ADHD
Chlorella Reduces Red Blood Cell Damage Linked to Cognitive Decline
Aerobic Exercise Boosts Cognitive Function, Brain Structure & Cardiovascular Health
Aerobic Exercise During Pregnancy Boosts Baby’s Brain
How Fiber and Friendly Flora Help Digestive Immunity
Anti-Aging Properties of Astaxanthin
Tocotrienols Stabilize Mast Cells
Q10, Zinc, and Antioxidants Needed During the Flu
Ubiquinol Q10 Anti-Aging Properties
Magnesium Intake Improves Insulin Resistance
Limonene Boosts Metabolism, Lowers Inflammation & Stress


Most Popular News:


Connect with Wellness Resources:

Connect on Facebook Follow us on Twitter Wellness Resources on Pinterest Wellness Resources YouTube Channel Get RSS News Feeds
Telecourse
bookstore
Thyroid and Metabolism
podcast
autoship