Featured Research

from universities, journals, and other organizations

New clues to inflammatory disease discovered

Date:
July 15, 2010
Source:
University of Florida
Summary:
Scientists studying two inflammation-related diseases, HIV and rheumatoid arthritis, identified changes in specific proteins linked to the action of macrophages, white blood cells that are key to the body's natural defenses. The findings could lead to early diagnosis tools and targeted therapy for diseases that stem from abnormal or uncontrolled macrophage activation, including cancer, cardiovascular disease and neurological disorders.

Immune system cells called macrophages spring into action to surround and destroy threats such as viruses or cancer cells. But sometimes the would-be protective response leads to persistent inflammation, which, in turn, can cause disease.

Related Articles


Scientists don't know exactly how macrophages cross the line from being good cops to bad cops, but researchers at the University of Florida recently unearthed several clues about the mechanisms involved. Through the lens of two inflammation-related diseases, HIV and rheumatoid arthritis, they identified changes in specific proteins linked to the action of macrophages, white blood cells that are key to the body's natural defenses.

The findings could lead to new early diagnosis tools and targeted therapy for diseases that stem from abnormal or uncontrolled macrophage activation, including cancer, cardiovascular disease and neurological disorders.

"Macrophage activation is important because it is involved in inflammation, which is involved in a number of diseases," said molecular biologist Maureen Goodenow, Ph.D., the Stephany W. Holloway university chair in AIDS research and professor of pathology, immunology and laboratory medicine in the UF College of Medicine, who led the research. "Chronically inflamed macrophages can be a problem for human health."

The findings, published in April and June in the journals AIDS and Cellular Immunology, built on studies also published in April by the group in the Journal of Leukocyte Biology.

With the advent of powerful antiretroviral therapies, people infected with HIV now survive for decades without progressing to AIDS. Even so, they battle inflammatory conditions such as HIV-associated dementia and cardiovascular disease.

One cause of macrophage activation that researchers are exploring is microbial translocation -- the spilling of parts of intestinal microbes into the blood circulation. Researchers have proposed that bacterial products thus released can activate immune system T cells and in so doing lead to the progression to AIDS.

One of those pathogen-related proteins spilled into the blood is called LPS. In studies of plasma and blood cells from people infected with HIV, the UF team investigated whether the amount of the protein present was associated with how quickly HIV progressed to AIDS. They found no correlation between the protein levels and depletion of T cells, the hallmark indicator of AIDS. Instead, they found that it was associated with activation of macrophages and their precursor cells, and with inflammation that persisted even after anti-viral therapy.

"This sets the stage to start teasing apart the relative contributions of different causes for immune activation in people with HIV," said Mark Wallet, Ph.D., an immunologist and postdoctoral researcher who is first author of two of the papers. "We can eventually use that information to better treat HIV-infected individuals by targeting the inflammation that causes so many long-term illnesses."

The researchers turned to rheumatoid arthritis to study the role of another molecule called interferon gamma. Produced in inflamed joints, it sets off an immune system process that is completed by a compound found in the natural lubrication fluid of joints. That compound has been shown to inhibit inflammation.

But it might also promote inflammation, the UF team has now shown. They found that in the presence of interferon gamma, the compound acted on macrophages to elevate production of two inflammation-causing proteins and suppress a protein that usually regulates normal immune cell responses.

"We're striving to dissect the initiating events that lead to chronic inflammation," Wallet said. "Immune cell activation and inflammation can become self-sustaining processes that are difficult to silence once a disease has progressed too far."

The researchers learned more about the roles of LPS and interferon gamma through a technique called proteomics, which gives a wealth of information that allows researchers to pinpoint specific changes within cells. It is a major shift from previous methods that rely on measuring secretions or biomarkers produced as a result of unspecified changes in cells.

"It's kind of like molecular archeology. We're getting pieces of a puzzle and trying to reconnect things in a biological context to infer what caused these events and get a better idea of what to focus on for future studies," said Joseph Brown, Ph.D., first author of one of the papers, who now works at Pacific Northwest National Laboratory in Richland, Wash. "What we're trying to do is better understand why the immune system is so off course, so exaggerated."

The work brings to light variations in protein expression patterns that relate to macrophage activation gone awry.

"This type of work is really critical to identifying specific fingerprints -- target proteins that could be either enhanced or suppressed," said Luis Montaner, D.V.M., M.Sc., D. Phil., editor-in-chief of the Journal of Leukocyte Biology and a professor of immunology at The Wistar Institute, who was not involved in the studies. "Getting a clear definition of what that means in the protein expression site can give the ability to target those proteins rather than the whole sequence."


Story Source:

The above story is based on materials provided by University of Florida. Note: Materials may be edited for content and length.


Cite This Page:

University of Florida. "New clues to inflammatory disease discovered." ScienceDaily. ScienceDaily, 15 July 2010. <www.sciencedaily.com/releases/2010/07/100715123420.htm>.
University of Florida. (2010, July 15). New clues to inflammatory disease discovered. ScienceDaily. Retrieved November 24, 2014 from www.sciencedaily.com/releases/2010/07/100715123420.htm
University of Florida. "New clues to inflammatory disease discovered." ScienceDaily. www.sciencedaily.com/releases/2010/07/100715123420.htm (accessed November 24, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Monday, November 24, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Winter Can Cause Depression — Here's How To Combat It

Winter Can Cause Depression — Here's How To Combat It

Newsy (Nov. 23, 2014) Millions of American suffer from seasonal depression every year. It can lead to adverse health effects, but there are ways to ease symptoms. Video provided by Newsy
Powered by NewsLook.com
Ebola-Hit Sierra Leone's Late Cocoa Leaves Bitter Taste

Ebola-Hit Sierra Leone's Late Cocoa Leaves Bitter Taste

AFP (Nov. 23, 2014) The arable district of Kenema in Sierra Leone -- at the centre of the Ebola outbreak in May -- has been under quarantine for three months as the cocoa harvest comes in. Duration: 01:32 Video provided by AFP
Powered by NewsLook.com
Don't Fall For Flu Shot Myths

Don't Fall For Flu Shot Myths

Newsy (Nov. 23, 2014) Misconceptions abound when it comes to your annual flu shot. Medical experts say most people older than 6 months should get the shot. Video provided by Newsy
Powered by NewsLook.com
WFP: Ebola Risks Heightened Among Women Throughout Africa

WFP: Ebola Risks Heightened Among Women Throughout Africa

AFP (Nov. 21, 2014) Having children has always been a frightening prospect in Sierra Leone, the world's most dangerous place to give birth, but Ebola has presented an alarming new threat for expectant mothers. Duration: 00:37 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins