Mechanisms regulating inflammation associated with type 2 diabetes, cancer identified

March 1, 2013, Boston University Medical Center

A study led by researchers at Boston University School of Medicine (BUSM) has identified epigenetic mechanisms that connect a variety of diseases associated with inflammation. Utilizing molecular analyses of gene expression in macrophages, which are cells largely responsible for inflammation, researchers have shown that inhibiting a defined group of proteins could help decrease the inflammatory response associated with diseases such as obesity, type 2 diabetes, cancer and sepsis.

The study, which is published online in the , was led by first author Anna C. Belkina, MD, PhD, a researcher in the department of microbiology at BUSM, and senior author Gerald V. Denis, PhD, associate professor of pharmacology and medicine at BUSM.

Epigenetics is an emerging field of study exploring how genetically identical cells express their genes differently, resulting in different phenotypes, due to mechanisms other than DNA sequence changes.

Previous studies have shown that a gene, called Brd2, is associated with high and excessive adipose (fat) tissue expansion that drives obesity when Brd2 levels are low and cancer when Brd2 levels are high. The Brd2 gene is a member of the Bromodomain Extra Terminal (BET) family of proteins and is closely related to Brd4, which is important in highly lethal carcinomas in young people, as well as in the replication of (HIV).

The BET family proteins epigenetically by acting on chromatin, the packaging material for genes, rather than on DNA directly. This mechanism of action is being explored because the interactions are not reflected in genome sequencing information or captured through DNA-based genetic analysis. In addition, this layer of has recently been shown to be a potential target in the development of novel epigenetic drugs that could target several diseases at once.

The study results show that proteins in the BET family have a strong influence on the production of pro-inflammatory cytokines in macrophages. This indicates that the defined family of proteins govern many aspects of acute inflammatory diseases, such as , sepsis and cardiovascular disease, among others, and that they should be explored as a potential target to treat a wide variety of diseases.

"Our study suggests that it is not a coincidence that patients with diabetes experience higher risk of death from cancer, or that patients with chronic inflammatory diseases, such as atherosclerosis and insulin resistance, also are more likely to be obese or suffer from inflammatory complications," said Belkina. "This requires us to think of diverse diseases of different organs as much more closely related than our current division of medical specialities allows."

Future research should explore how to successfully and safely target and inhibit these proteins in order to stop the inflammatory response associated with a variety of diseases.

Explore further: Researchers identify key regulator of inflammatory response

Related Stories

Researchers identify key regulator of inflammatory response

April 12, 2012
(Medical Xpress) -- Researchers at Boston University School of Medicine (BUSM) have identified a gene that plays a key role in regulating inflammatory response and homeostasis. These findings could help lead to the development ...

Scientists find underlying mechanisms behind chronic inflammation-associated diseases

February 23, 2013
(Medical Xpress)—Inflammatory response plays a major role in both health protection and disease generation. While the symptoms of disease-related inflammatory response have been know, scientists have not understood the ...

A small cut with a big impact

May 2, 2012
Diseases and injuries trigger warning signals in our cells. As a result, genes are expressed and proteins produced, modified or degraded to adapt to the external danger and to protect the organism. In order to be able to ...

Recommended for you

Genomics reveals key macrophages' involvement in systemic sclerosis

January 18, 2018
A new international study has made an important discovery about the key role of macrophages, a type of immune cell, in systemic sclerosis (SSc), a chronic autoimmune disease which currently has no cure.

First vaccine developed against grass pollen allergy

January 18, 2018
Around 400 million people worldwide suffer in some form or other from a grass pollen allergy (rhinitis), with the usual symptoms of runny nose, cough and severe breathing problems. In collaboration with the Viennese firm ...

Researchers discover key driver of atopic dermatitis

January 17, 2018
Severe eczema, also known as atopic dermatitis, is a chronic inflammatory skin condition that is driven by an allergic reaction. In their latest study, researchers at La Jolla Institute reveal an important player that promotes ...

Who might benefit from immunotherapy? New study suggests possible marker

January 16, 2018
While immunotherapy has made a big impact on cancer treatment, the fact remains that only about a quarter of patients respond to these treatments.

Researchers identify new way to unmask melanoma cells to the immune system

January 16, 2018
system, which enables these deadly skin cancers to grow and spread.

How the immune system's key organ regenerates itself

January 15, 2018
With advances in cancer immunotherapy splashing across headlines, the immune system's powerful cancer assassins—T cells—have become dinner-table conversation. But hiding in plain sight behind that "T" is the organ from ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.