Featured Research

from universities, journals, and other organizations

Protein could offer target to reduce lung damage from smoking-caused emphysema

Date:
May 17, 2011
Source:
Indiana University School of Medicine
Summary:
An international research team has identified a lung protein that appears to play a key role in smoking-related emphysema and have crafted an antibody to block its activity.

An international research team has identified a lung protein that appears to play a key role in smoking-related emphysema and have crafted an antibody to block its activity, Indiana University scientists reported.

The research, conducted in mice, suggests that the protein, a cytokine named EMAPII, could provide a target for drugs to treat emphysema, said Irina Petrache, M.D., associate professor of medicine at the Indiana University School of Medicine. The research was posted online May 16 for the June edition of The Journal of Clinical Investigation.

Emphysema, a form of chronic obstructive pulmonary disease (COPD) that affects nearly 5 million people in the U.S alone, is caused by the destruction of cells that transfer oxygen from the lungs to the blood, along with inflammation in the lungs. Cigarette smoking is the most common cause of emphysema.

The cytokine EMAPII -- a type of cell-signaling molecule -- is normally part of the process of early lung development. Research had previously found that EMAPII could cause the death of cells that line blood vessels -- endothelial cells -- and inflammation, but it had not been identified as the molecular culprit at work when cigarette smoking inflicted its damage on the lungs.

"The fact that we could have a single target affecting two major processes made us excited about looking for it in response to smoking," said Dr. Petrache, the Floyd and Reba Smith Investigator in Respiratory Disease at IU.

When the researchers induced emphysema in mice exposed to cigarette smoke, tests showed the mice had elevated levels of the EMAPII cytokine. In other tests, the scientists also found elevated levels of the cytokine in the lungs of patients with COPD.

The researchers also found that the cell death caused by the EMAPII resulted in the release of enzymes that cause more production of EMAPII, causing a vicious cycle of elevated cytokine levels and more cell death.

Members of the research team, led by first author Matthias Clauss, Ph.D., IU associate research professor of cellular and integrative physiology, created an antibody designed to specifically target EMAPII and block its activity. The mice received an inhaled version of the antibody during their third month of smoking. They then were exposed to a fourth month of smoking without the treatment.

The mice receiving the treatment had significantly less cell death and inflammation and improved lung function compared to the smoking mice who did not receive the treatment. Moreover the benefits to the treated mice continued even after the treatment stopped.

Next steps include optimizing the duration of the antibody treatments to determine whether they continue to have an effect after the animals have stopped smoking, she said. Plans also call for work to measure levels of the cytokine in large numbers of human emphysema and COPD patients to determine whether it can be used as a biomarker to measure the presence, severity or type of lung disease.

Considerable research work remains before an EMAPII antibody might be ready for testing in humans, Dr. Petrache said.

Additional researchers on the project included Robert Voswinckel and Sandeep Nikam of the Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany; Gangaraju Rajashekhar, Ninotchka L. Sigua, Natalia I. Rush, Kelly S. Schweitzer, Krzysztof Kamocki, Amanda J. Fisher, Yuan Gu, Bilal Safadi, Homer L. Twigg III and Robert G. Presson of the IU School of Medicine; Heinz Fehrenbach of the Leibniz Center for Medicine and Biosciences, Borstel, Germany; Ali . Yildirim of the German Research Center for Environmental Health, Helmholtz Zentrum, Munich, Germany; Walter C. Hubbard of the Johns Hopkins University, Baltimore; Rubin M. Tuder of the University of Colorado Health Science Center, Denver; and Sanjay Sethi of New York University School of Medicine.

Funding for the research was provided by the National Institutes of Health, Deutsche Forschungsgemeinschaft, the German Clusters of Excellence initiative and the European Commission.


Story Source:

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


Journal Reference:

  1. Matthias Clauss, Robert Voswinckel, Gangaraju Rajashekhar, Ninotchka L. Sigua, Heinz Fehrenbach, Natalia I. Rush, Kelly S. Schweitzer, Ali . Yildirim, Krzysztof Kamocki, Amanda J. Fisher, Yuan Gu, Bilal Safadi, Sandeep Nikam, Walter C. Hubbard, Rubin M. Tuder, Homer L. Twigg, Robert G. Presson, Sanjay Sethi, Irina Petrache. Lung endothelial monocyte-activating protein 2 is a mediator of cigarette smoke–induced emphysema in mice. Journal of Clinical Investigation, 2011; DOI: 10.1172/JCI43881

Cite This Page:

Indiana University School of Medicine. "Protein could offer target to reduce lung damage from smoking-caused emphysema." ScienceDaily. ScienceDaily, 17 May 2011. <www.sciencedaily.com/releases/2011/05/110516162149.htm>.
Indiana University School of Medicine. (2011, May 17). Protein could offer target to reduce lung damage from smoking-caused emphysema. ScienceDaily. Retrieved July 31, 2014 from www.sciencedaily.com/releases/2011/05/110516162149.htm
Indiana University School of Medicine. "Protein could offer target to reduce lung damage from smoking-caused emphysema." ScienceDaily. www.sciencedaily.com/releases/2011/05/110516162149.htm (accessed July 31, 2014).

Share This




More Health & Medicine News

Thursday, July 31, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Health Insurers' Profits Slide

Health Insurers' Profits Slide

Reuters - Business Video Online (July 30, 2014) Obamacare-related costs were said to be behind the profit plunge at Wellpoint and Humana, but Wellpoint sees the new exchanges boosting its earnings for the full year. Fred Katayama reports. Video provided by Reuters
Powered by NewsLook.com
Concern Grows Over Worsening Ebola Crisis

Concern Grows Over Worsening Ebola Crisis

AFP (July 30, 2014) Pan-African airline ASKY has suspended all flights to and from the capitals of Liberia and Sierra Leone amid the worsening Ebola health crisis, which has so far caused 672 deaths in Guinea, Liberia and Sierra Leone. Duration: 00:43 Video provided by AFP
Powered by NewsLook.com
At Least 20 Chikungunya Cases in New Jersey

At Least 20 Chikungunya Cases in New Jersey

AP (July 30, 2014) At least 20 New Jersey residents have tested positive for chikungunya, a mosquito-borne virus that has spread through the Caribbean. (July 30) Video provided by AP
Powered by NewsLook.com
Xtreme Eating: Your Daily Caloric Intake All On One Plate

Xtreme Eating: Your Daily Caloric Intake All On One Plate

Newsy (July 30, 2014) The Center for Science in the Public Interest released its 2014 list of single meals with whopping calorie counts. Video provided by Newsy
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:
from the past week

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