University of Michigan researchers identify cells resistant to asthma treatments – AnnArbor.com


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University of Michigan researchers identify cells resistant to asthma treatments
AnnArbor.com
Researchers at the University of Michigan Health System have discovered the type of cell that appears to cause asthma symptoms even when treated by medicine from an inhaler. The findings may help scientists develop new treatment options,
Scientists discover new type of cell with a key role in treatment-resistant asthmaMarketWatch (press release)

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Molecular Pathway, Asthma Inflammation and Future Treatment Options

Researchers Identify Molecular Pathway that leads to Inflammation in Asthma

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.”

Co-authors include Jinming Zhao, Ph.D., Silvana Balzar, M.D., Claudette M. St. Croix, Ph.D., and John B. Trudeau, B.S., of UPSOM and the Asthma Institute; and Valerie B. O’Donnell Ph.D., of Cardiff University, United Kingdom. The study was funded by the National Institutes of Health and the American Heart Association.

Contact: Anita Srikameswaran
SrikamAV@upmc.edu
412-578-9193
University of Pittsburgh Schools of the Health Sciences
Pitt team finds molecular pathway that leads to inflammation in asthma
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Scientists Identify Seven Genes Associated with Childhood Asthma – TopNews United States


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Scientists Identify Seven Genes Associated with Childhood Asthma
TopNews United States
A new study conducted by British researchers has claimed to find seven genes associated with childhood asthma and concluded that allergies are not the cause
Genetic study could aid new asthma treatmentsWebMD.Boots.com
Complex Asthma Genes Not Useful for Setting RiskMedPage Today
Drugs 'could target asthma genes'BBC News
Daily Mail –Mirror.co.uk –Insciences Organisation
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Scientists Identify Brain Circuits Related to the Initiation and Termination of Movement Sequences in NIH-Supported Study

In humans, throwing a ball, typing on a keyboard, or engaging in most other physical activities involves the coordination of numerous discrete movements that are organized as action sequences. Scientists at the National Institutes of Health and the Gulbenkian Institute in Portugal have identified brain activity in mice that can signal the initiation and termination of newly learned action sequences. The findings appear online today in the current issue of Nature.

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