Researchers Discover Mechanism in cells that leads to Inflammatory Diseases

Los Angeles, March 12, 2012 – Cedars-Sinai researchers have unlocked the mystery of how an inflammatory molecule is produced in the body, a discovery they say could lead to advances in the treatment of rheumatoid arthritis, Type 2 diabetes and numerous other chronic diseases that affect tens of millions of people.

The study, funded by the National Institutes of Health, is published online by the peer-reviewed journal Immunity and will appear in the March print edition.

The researchers identified for the first time the mechanism that leads to the production of the molecule interleukin-1beta. It is a major contributor to inflammation, which lies at the root of many serious health conditions, including atherosclerotic heart disease and some types of strokes.

Current drug therapies seek to block this molecule's action after it is secreted by cells. However, the new research could lead to the development of treatments that would prevent the body from producing it, resulting in more effective medications and therapies for inflammatory diseases.

"If we understand how this molecule is made in the body, we may be able to block it before it is produced," said study author Dr. Moshe Arditi, executive vice chair of research in the Department of Pediatrics and director of the Division of Pediatric Infectious Diseases and Immunology. "Until now, this was the missing piece of the puzzle."

Arditi, who also directs Cedars-Sinai's Infectious and Immunologic Diseases Research Center, found that damaged mitochondrial DNA activate specific proteins within dying cells, triggering the release of interleukin-1beta. Previous research has shown the molecule, when over-secreted by cells, can be a significant contributor to major inflammatory diseases.

Three of these diseases alone -- atherosclerosis, Type 2 diabetes and rheumatoid arthritis – affect an estimated 100 million Americans.

Arditi is planning further studies to build on the findings.


"The discovery by Arditi and colleagues has great potential to impact a wide range of inflammatory diseases, particularly in their early stages where an intervention could prevent more severe and debilitating ravages of such diseases," said Dr. Leon Fine, Cedars-Sinai's vice dean of research and chair of biomedical sciences. "This discovery, at last, may open the door to such therapy."


In addition to Cedars-Sinai, other research groups involved in the study include UCLA 's David Geffen School of Medicine, UC Merced's Health Sciences Research Institute and School of Natural Sciences; UC Riverside's Department of Chemistry and the University of Massachusetts Medical School's Department of Medicine.

http://www.proventus.org.uk/page636.html

Researchers Discover How Vitamin D Inhibits Inflammation

Researchers at National Jewish Health have discovered specific molecular and signalling events by which vitamin D inhibits inflammation. In their experiments, they showed that low levels of Vitamin D, comparable to levels found in millions of people, failed to inhibit the inflammatory cascade, while levels considered adequate did inhibit inflammatory signalling. They reported their results in the March 1, 2011, issue of The Journal of Immunology.

“This study goes beyond previous associations of vitamin D with various health outcomes. It outlines a clear chain of cellular events, from the binding of DNA, through a specific signalling pathway, to the reduction of proteins known to trigger inflammation,” said lead author Elena Goleva, assistant professor of paediatrics at National Jewish Health. “Patients with chronic inflammatory diseases, such as asthma, arthritis and prostate cancer, who are vitamin D deficient, may benefit from vitamin D supplementation to get their serum vitamin D levels above 30 nanograms/milliliter.”

Current national guidelines suggest that people should maintain a minimum blood serum level of 20 ng/ml, although there is much scientific debate about optimum levels. Vitamin D has long been known to contribute to bone health by promoting the absorption of calcium. In recent years, much attention has been paid to its possible immune and inflammatory benefits. Low vitamin D levels have been associated with several diseases including asthma, cancer, diabetes, and arthritis.


In the current study researchers examined the specific mechanisms by which vitamin D might act on immune and inflammatory pathways. They incubated human white blood cells with varying levels of vitamin D, then exposed them to lipopolysaccharide (LPS), a molecule associated with bacterial cell walls that is known to promote intense inflammatory responses.


Cells incubated with no vitamin D and in solution containing 15 ng/ml of vitamin D produced high levels of cytokines IL-6 and TNF-alpha, major actors in the inflammatory response. Cells incubated in 30 ng/ml vitamin D and above showed significantly reduced response to the LPS. The highest levels of inflammatory inhibition occurred at 50 ng/ml.


Through a complex series of experiments, the researchers identified a new location where the vitamin-D receptor appears to bind directly to DNA and activate a gene known as MKP-1. MKP-1 interferes with the inflammatory cascade triggered by LPS, which includes a molecule known as p38, and results in higher levels of IL-6 and TNF-alpha.


“This newly identified DNA-binding site for the vitamin-D receptor, and the specific pathways inhibited by higher levels of vitamin D provide a plausible mechanism for many of the benefits that have been associated with vitamin D,” said Dr. Goleva. ‘The fact that we showed a dose-dependent and varying response to levels commonly found in humans also adds weight to the argument for vitamin D’s role in immune and inflammatory conditions.”

Source - National Jewish Health - Internet PageRef - Yong Zhang, Donald Y. M. Leung, Brittany N. Richers, Yusen Liu, Linda K. Remigio, David W. Riches, And Elena Goleva. Vitamin D Inhibits Monocyte/Macrophage Proinflammatory Cytokine Production by Targeting MAPK Phosphatase-1. The Journal of Immunology, March 1, 2012 DOI: 10.4049/%u200Bjimmunol.1102412

http://www.proventus.org.uk/page656.html

Inflammation

Uncovering whether or not you are suffering from unseen inflammation in your body is quite important because it is an underlying factor associated with many diseases. Disease processes can be affected or caused by inflammation.

If your immune system’s ability to quell inflammation is impaired you may be heading toward illness and premature aging.

Addressing the cause [s] of inflammation and learning how to live an anti-inflammatory lifestyle can assist in supporting your health.

There are normal and appropriate inflammatory responses of the immune -defence system -- to infection and trauma. This kind of inflammation is necessary. It is needed it to survive and works to determine friend from foe.

An immediate inflammatory reaction generated by your body’s immune system is known as an “acute inflammatory reaction”

When your immune system becomes uncontrolled, for whatever reason, it will attack the bodies healthy tissues resulting in autoimmune diseases and chronic, underlying inflammation which can slowly damages your organs / tissues reducing your ability to function optimally.

It is postulated that chronic inflammation will also lead to premature aging.

Anti-inflammatory drugs are often useful for acute problems, however they do interfere with the body's own immune response and cause adverse side effects especially with long term use.

Illness - ill-health - ailments

A state of poor health is sometimes thought to be another word for disease. However illness may be considered to the subjective perception of a person’s experience [s] of the symptoms of an objectively defined disease or condition.

The state of being healthy includes not merely the absence of disease and feeling ill, it may be considered to be a state of complete physical, mental and social well-being. When these conditions are not fulfilled, then the person can be considered to be experiencing an illness or to be ill.

Signs and symptoms

A symptom or symptoms of a condition is that which the person experiences it is how they feel.

A sign or signs of a condition is that which is observed and noted by the health professional [s] which provides indications of the condition [s] and enables them to diagnose the problem and prescribe the appropriate medication [s].

Taking preventative action to assist in the health process is not the same as taking action to combat a serious disease. If you are unfortunate enough to experience unusual symptoms, no matter how vague, you must must consult a health professional. If you are unfortunate enough to meet with an unsympathetic health professional then consult another.

Never delay early diagnosis and early intervention is imperative.

Taking action to counter inflammation will help you to establish a better level of health and by so doing assist your body in combating any disease problems.

Remember in the case of serious diseases it is never a cure.

Whole Foods - Eat high-fibre, plant-based diets, which are inherently anti-inflammatory.

Healthy Fats - Eat healthy monounsaturated fats in olive oil, nuts and avocados, and getting omega-3 fats from small fish like sardines, herring, and wild salmon.

Regular Exercise - Regular exercise reduces inflammation. It also improves immune function, strengthens your cardiovascular systems, corrects and prevents insulin resistance. It is key for improving your mood and erasing the effects of stress. When exercising play music that you enjoy.

Relax - Your whole body and lower inflammation when you practice yoga or meditation, breathe well, take a hot bath.

Heal Your Gut -- Take biotic to help your digestion and improve the balance of healthy bacteria in your gut, which reduces inflammation.

Supplement -- Take a multivitamin/multi-mineral supplement, fish oil, and vitamin D, may help reduce inflammation.

Avoid Allergens -- If you have food allergies, find out what you're allergic to.

Anti-inflammatory refers to the property of a substance or treatment that reduces inflammation.

Some advocate the consumption of anti-inflammatory foodstuffs as a means of influencing inflammation. A typical anti-inflammatory diet includes a well-balanced, varied diet high in vegetables and low in refined carbohydrates and fats.

Anti-inflammatory foods include most colourful fruits and vegetables, oily fish, nuts, seeds, and certain spices and herbs.

A diet high in vegetables and low in refined carbohydrates and saturated and trans fats may enhance the creation of prostaglandins.

There are three main types of prostaglandins: PG-E1 and PG-E3, which have anti-inflammatory properties, and PG-E2, which promotes inflammation.

Omega-3 fatty acids have been shown to disrupt inflammation cell signalling pathways by binding to the GPR120 receptor.

http://www.proventus.org.uk/page774.html

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