Navigation Links
Pitt team finds molecular pathway that leads to inflammation in asthma
Date:8/8/2011

PITTSBURGH, Aug. 8 Researchers at the University of Pittsburgh School of Medicine have identified a molecular pathway that helps explain how an enzyme elevated in asthma patients can lead to increased mucus production and inflammation that is characteristic of the lung condition. Their findings, reported online in this week's Proceedings of the National Academy of Sciences, reveal unique interactions between biological molecules that could be targeted to develop new asthma treatments.

An enzyme called epithelial 15-lipoxygenase 1 (15LO1) metabolizes fatty acids to produce an eicosanoid known as 15 hydroxyeicosaetetranoic acid (15 HETE) and is elevated in the cells that line the lungs of asthma patients, explained Sally E. Wenzel, M.D., professor of medicine, Pitt School of Medicine, and director of the Asthma Institute at UPMC and Pitt School of Medicine. Her team showed in 2009 that the enzyme plays a role in mucus production.

"In this project, we found out 15 HETE is conjugated to a common phospholipid," she said. "That complex, called 15HETE-PE, and 15LO1 behave as signaling molecules that appear to have a powerful influence on airway inflammation."

By examining lung cells obtained by bronchoscopy from 65 people with asthma, the researchers found that both 15LO1 and 15HETE-PE displace an inhibitory protein called PEBP1 from its bond with another protein called Raf-1, which when freed can lead to activation of extracellular signal-regulated kinase(ERK). Activated ERK is commonly observed in the epithelial, or lung lining, cells in asthma, but until now the reason for that was not understood.

"This is an important study as it directly explores the important role of 15-lipoxygenase 1 in the airway epithelial cells of patients with asthma, which immediately establishes the relevance to human disease," said Mark T. Gladwin, M.D., chief, Division of Pulmonary, Allergy and Critical Care Medicine, UPSOM.

Other experiments showed that knocking down 15LO1 decreased the dissociation of Raf-1 from PEBP1, which in turn reduced ERK activation. The pathway ultimately influences the production of factors involved in inflammation and mucus production.

"These results show us on both a molecular and mechanistic level and as mirrored by fresh cells from the patients themselves that the epithelial cells of people with asthma are very different from those that don't have it," Dr. Wenzel said. "It also gives us a potential treatment strategy: If we can prevent Raf-1 displacement, we might have a way of stopping the downstream consequences that lead to asthma."


'/>"/>

Contact: Anita Srikameswaran
SrikamAV@upmc.edu
412-578-9193
University of Pittsburgh Schools of the Health Sciences
Source:Eurekalert

Related biology news :

1. Research finds veterinary medicine students experience higher depression levels than peers
2. High-throughput screen finds compounds that regulate cancer cell invasion
3. Study finds some desert birds less affected by wildfires and climate change
4. Cancer stem cells recruit normal stem cells to fuel ovarian cancer, U-M study finds
5. Behavioral treatment for migraines a cost-effective alternative to meds, study finds
6. Study finds pregnancy and birth environment may affect development of autism in twins
7. Scripps study finds plastic in 9 percent of garbage patch fishes
8. Study finds golden algae responsible for killing millions of fish less toxic in sunlight
9. Study finds widespread stream biodiversity declines at low levels of urban development
10. Pregnant women can prevent excess weight gain with simple steps, study finds
11. Study finds copper proves effective against new E. coli strains
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:1/27/2016)... , Jan. 27, 2016  Rite Track, Inc. ... in West Chester, Ohio announced ... winning service staff, based in Austin, Texas ... and ability to provide modifications, installations and technical support ... , CEO of PLUS, commented, "PLUS has provided world ...
(Date:1/21/2016)... , January 21, 2016 ... to a new market research report "Emotion Detection and ... Others), Software Tools (Facial Expression, Voice Recognition and ... - Global forecast to 2020", published by MarketsandMarkets, ... expected to reach USD 22.65 Billion by 2020, ...
(Date:1/15/2016)... SAN JUAN, Puerto Rico , Jan. 15, 2016 ... forcing companies big and small to find new ways ... data driven culture. iOS and ... their device based on biometrics, transforming it into a ... can request that users swipe their fingerprint on their ...
Breaking Biology News(10 mins):
(Date:2/10/2016)... ... February 10, 2016 , ... ... states, announced today the promotion of two long-standing principal investigators (PI) to the ... Medicine, Clinical Research and Development. , Dr. Laurence Chu, a Benchmark Research PI ...
(Date:2/10/2016)... ... February 10, 2016 , ... PatientCrossroads ... built on the secure online PatientCrossroads platform, has exceeded both its one-year and ... joined the PROMPT study, which seeks to advance understanding of the hereditary risks ...
(Date:2/10/2016)... ... February 09, 2016 , ... ... current winner of the Highest Overall Customer Rating Award from Circuits Assembly , ... business units across the USA, Canada, Mexico and China. , The EMS provider, ...
(Date:2/9/2016)... , ... February 08, 2016 , ... ... testing services, announced today the launch of its revamped and improved website. In ... language service solutions, the redesigned website will better communicate how the company designs ...
Breaking Biology Technology: