Nav: Home

Turning off asthma attacks

December 02, 2016

Working with human immune cells in the laboratory, Johns Hopkins researchers report they have identified a critical cellular "off" switch for the inflammatory immune response that contributes to lung-constricting asthma attacks. The switch, they say, is composed of regulatory proteins that control an immune signaling pathway in cells.

"Asthma patients are constantly firing through this pathway because those proteins are stuck in the 'on' position, without proper control by other proteins that shut down this reaction," says Nicola Heller, Ph.D., assistant professor of anesthesiology and critical care medicine at the Johns Hopkins University School of Medicine.

Asthma has been correlated with an overabundance of one type of immune cell called M2 macrophages in the lungs. In a nonasthmatic person, the M2 macrophages activate to clean up inhaled allergens and foreign particles, and then deactivate when the irritant is broken down.

However, in people with asthma, the M2 cells and the chemical signals they emit linger and call in other cells that cause inflammation that can trigger an asthma attack with the classic symptoms of difficulty breathing, wheezing and shortness of breath. Over time, the lung is changed by secretions from the M2 cells, which cause the lung tissue to remodel itself, contributing to irreversible obstruction and poor lung function. "If you prevent these cells from becoming the M2 type, you can potentially stop the continued inflammation and long-term structural changes," says Heller.

The new research, reported Nov. 25 in the Journal of Biological Chemistry, investigated the role of two proteins, GRB10 and p70S6K, in the control of the signaling pathway that activates M2 cells.

In their previous work, also published in the Journal of Biological Chemistry Sept. 23, Heller's group found that the inflammatory pathway involving the two proteins begins with interleukin 4 (IL-4), an immune system chemical that passes through a protein named IRS-2 before activating the M2 cells. They found that other proteins that stop the action of IRS-2 were not present in human M2 cells from people with allergies compared to healthy people. This made IRS-2 more active and increased the formation of M2 cells in people with allergies.

In the new study, Heller's lab delved deeper into the IRS-2 pathway. By analyzing chemical changes of the IRS-2 protein in immortalized cultures of human white blood cells, it determined that IRS-2 appeared in two different forms -- "on," which allows the signal to pass through, and "off," which stops the signal from activating the cells into M2 macrophages. They began by observing which proteins became active in the presence of IL-4 in human white blood cells and add "stop" signals to IRS-2. The activity of two regulatory proteins, GRB10 and p70S6K, increased after IL-4 exposure compared to the same cells that were not exposed to IL-4.

In further test tube experiments, the researchers treated the immortalized white blood cells with both chemical and genetic blockers, called small interfering RNA (siRNA), designed to render either p70S6K or GRB10 nonfunctional. The researchers saw that decreased GRB10 and p70S6K activity resulted in more of the "on" form of IRS-2, meaning these proteins are responsible for turning off IRS-2 and thereby downstream M2 production.

"This confirmed for us that without properly functioning GRB10 and p70S6K, the cells could not turn off IRS-2 signaling and M2 production," says Heller.

The research team, Heller says, has already begun experiments to further explore the implications of these results, which include looking at differences in this pathway between cells taken from allergic and healthy individuals, and testing the efficacy of an inhalable drug that mimics the function of GRB1 and p70S6K to shut off the development of M2 macrophages in the lungs of mice. "One of the advantages of working with lung macrophages is that they are one of the first cells that see anything that gets put in an inhaler," says Heller. "So we hope to modulate their activity in this way."

These findings also have implications for treatment of cancer and other disorders, such as obesity, in which M2 macrophage cells play a regulatory role in tumor growth and fat deposition.
-end-
Other researchers involved in this study include Kristi J. Warren, Xi Fang, Nagaraj M. Gowda and Joshua Thompson of the Johns Hopkins University School of Medicine.

This work was funded by the National Institutes of Health Pathway to Independence Award (K99/R00 HL096897).

Johns Hopkins Medicine

Related Asthma Articles:

Insomnia prevalent in patients with asthma
A team of researchers from the University of Pittsburgh has found that insomnia is highly prevalent in adults with asthma and is also associated with worse asthma control, depression and anxiety symptoms and other quality of life and health issues.
Test used to diagnose asthma may not be accurate
A new study urges caution in the use of the mannitol challenge test for asthma in non-clinical settings.
Turning off asthma attacks
Working with human immune cells in the laboratory, Johns Hopkins researchers report they have identified a critical cellular 'off' switch for the inflammatory immune response that contributes to lung-constricting asthma attacks.
Access to asthma meds, plus flu vaccines, keep kids with asthma healthy
Kids need flu shots to prevent asthma flares, and medications available in school to keep 86 percent in class, according to two studies being presented at the American College of Allergy, Asthma and Immunology Annual Scientific Meeting.
Discovery could lead to better asthma treatment
Scientists have made a discovery that could lead to improved treatment for asthma sufferers.
Do asthma and COPD truly exist?
Defining a patient's symptoms using the historical diagnostic labels of asthma and chronic obstructive pulmonary disease (COPD) is an outdated approach to understanding an individual's condition, according to experts writing in the European Respiratory Journal today.
Asthma in many adolescents is not an allergic disease
New research indicates that asthma in many adolescents is not likely to involve inflammation of the airways and therefore should not be considered an allergic disease.
First classification of severe asthma
Severe asthma can have a devastating effect on sufferers, affecting their ability to work or go to school and to lead normal lives.
Exploring 'clinical conundrum' of asthma-COPD overlap in nonsmokers with chronic asthma
Researchers may be closer to finding the mechanism responsible for loss of lung elastic recoil and airflow limitation in nonsmokers with chronic asthma.
Asthma app helps control asthma: Alerts allergists when sufferers need assistance
New study in Annals of Allergy, Asthma and Immunology shows how an app directly connecting an allergist and an asthma sufferer can provide necessary intervention when asthma isn't under control.

Related Asthma Reading:

Asthma-Free Naturally: Everything You Need to Know to Take Control of Your Asthma - Featuring the Buteyko Breathing Method Suitable for Adults and Children
by Patrick McKeown MA (Author)

This revolutionary book teaches readers how to take control of their asthma safely and effectively without any side effects. The approach encompasses the Buteyko Breathing Method as well as guidance on diet, sleep, physical activity, and other lifestyle changes that can provide a natural alternative to Asthma medications. The author was a chronic asthmatic who applied the Buteyko Breathing Method to free himself from his asthma condition. In this book, he details the Buteyko Breathing Method and provides guidance on diet, sleep, physical activity, and other lifestyle changes that can provide... View Details


Asthma For Dummies
by William E. Berger (Author), Jackie Joyner-Kersee (Foreword)

The incidence of asthma is rising dramatically in the United States and across the globe. Asthma affects 17 million people in the U.S. and is the most common chronic childhood disease. If you or someone you love suffers from asthma, you know that there is no cure—however, with proper care, asthmatics can lead normal, active, and fulfilling lives. Now you can breathe easy with this plain-English guide, which clearly explains the prevention, diagnosis, symptoms, and treatment of the disease.

Asthma For Dummies will help asthma sufferers and their loved ones get a strong handle on... View Details


The Allergy and Asthma Cure: A Complete 8-Step Nutritional Program
by Fred Pescatore M.D. (Author)

Free yourself of allergies and asthma once and for all with Dr. Pescatore's breakthrough program

"" Dr. Fred Pescatore's The Allergy and Asthma Cure reveals a unique and revolutionary understanding of the underlying conditions of allergy and asthma-from food triggers to the environment to nutritional deficiencies. His integrative program of both alternative and traditional treatments can dramatically improve health and vitality, safely and soundly. This book will have a prominent place in my library and I highly recommend it! ""
-Ann Louise Gittleman, Ph.D., C.N.S., author of the... View Details


The Asthma Educator's Handbook
by Christopher H. Fanta (Author), Elisabeth S. Stieb (Author), Elaine L. Carter (Author), Kenan E. Haver (Author)

Learn asthma care essentials -- from top experts at the Partners Asthma Center

"This book teaches physicians and other healthcare professionals how to recognize and treat asthma exacerbations and was inspired by patients and their experiences with this disease. It is designed for informed educators who know a fair amount about asthma while focusing on patient needs. It is an excellent resource for asthma educators. 3 Stars."--Doody's Review Service

Internists, family physicians, physician's assistants, respiratory therapists, and pharmacists will find this... View Details


Breathe to Heal: Break Free From Asthma (Learn Buteyko) (Breathing Normalization)
by Sasha Yakovleva (Author), K.P. Buteyko MD-PhD (Author), A.E. Novozhilov MD (Author), Victor Lunn-Rockliffe (Illustrator), Arash Akhgari (Illustrator), Jane E. Brody (Illustrator), Thomas Fredricksen (Illustrator), Ira J. Packman (Illustrator), Jean Boles (Illustrator)

Understand Asthma & Breathing Problems. Stop fighting against asthma attacks and breathing difficulties! Say "Goodbye" to breathing problems! This book will help asthma sufferers to establish natural and wholesome breathing patterns and prevent asthma attacks. It will provide you with the information you need to tame your or your child's breathing difficulties naturally by improving the function of the respiratory system. It contains comprehensive instructions on the Breathing Normalization method based on the discovery by Dr. Buteyko in 1952 in Russia. Since then, this commonly called... View Details


ASTHMA: A Fresh Approach To Dealing With Asthma
by Ronnie Smith (Author)

What Everyone Needs To Know About This Fresh Approach To Dealing With Asthma... The most brilliant minds in the fields of health, medicine and psychology have tried and failed to find the solution to Asthma.  Now, a new approach based on going back to nature rather than man-made medicine is gaining ground throughout the world. This "fresh approach" was initially laughed at and thought to be a joke.  But when people started to have incredible results with it the laughter stopped.  Now more and more research is gradually being done on this new nutritional approach to dealing with this... View Details


Living a Healthy Life with Chronic Conditions: Self-Management of Heart Disease, Arthritis, Diabetes, Depression, Asthma, Bronchitis, Emphysema and Other Physical and Mental Health Conditions
by Kate Lorig DrPH (Author), Halsted Holman MD (Author), David Sobel MD MPH (Author), Diana Laurent MPH (Author), Virginia González MPH (Author), Marion Minor PT PhD (Author)

Completely redesigned for easy reading and fully updated with the latest research and information on current practice, medication, legal matters, and specific conditions, this new edition of a vital resource is full of tips, suggestions, and strategies to deal with chronic illness and symptoms, such as fatigue, pain, shortness of breath, disability, and depression. It encourages readers to develop individual approaches to setting goals, making decisions, and finding resources and support so that they are able to do the things they want and need. Originally based on a five-year study conducted... View Details


The Lion Who Had Asthma (Albert Whitman Prairie Paperback)
by Jonathan London (Author), Nadine Bernard Westcott (Illustrator)

Sean likes to pretend he's a lion, roaring in the jungle. But this lion starts to cough, his chest hurts, and it's hard to breathe. This lion has asthma. So Sean's mother gives him his medicine to help him breath. Now Sean imagines he's a jet pilot. View Details


Asthma
by John Hankiewicz (Illustrator)

Asthma is a collection of recent comics by John Hankiewicz. From story to story, even page to page, the book mixes a startling range of graphic and narrative styles to form a dreamlike whole.

“Amateur Comics” creates a wordless lyric of body, chairs, and space. “Martha Gregory” delves into the rhyming psyches of a young woman and an old man. “Jazz” charts a single day through the lens of the unconscious. Also included are the visually abstract “The Kimball House,” the autobiographical “Westmont Is Next,” the elliptically humorous “Dance” (printed in black and red),... View Details


Healing the New Childhood Epidemics: Autism, ADHD, Asthma, and Allergies: The Groundbreaking Program for the 4-A Disorders
by Kenneth Bock (Author), Cameron Stauth (Author)

Autism is an epidemic: It has spiked 1,500 percent in the last twenty years. ADHD, asthma and allergies have also skyrocketed over the same time period. One of these conditions now strikes one in every three children in America. But there is hope. Leading medical innovator Kenneth Bock, M.D., has helped change the lives of more than a thousand children, and in this important book, with a comprehensive program that targets all four of the 4-A disorders, he offers help to children everywhere. This is the book that finally puts hope within reach.

Doctors have generally overlooked the... View Details

Best Science Podcasts 2018

We have hand picked the best science podcasts for 2018. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

The Big Five
What are the five biggest global challenges we face right now — and what can we do about them? This hour, TED speakers explore some radical solutions to these enduring problems. Guests include geoengineer Tim Kruger, president of the International Rescue Committee David Miliband, political scientist Ian Bremmer, global data analyst Sarah Menker, and historian Rutger Bregman.
Now Playing: Science for the People

#457 Trowel Blazing
This week we look at some of the lesser known historical figures and current public perception of anthropology, archaeology, and other fields that end in "ology". Rebecca Wragg Sykes, an archaeologist, writer, and co-founder of the TrowelBlazers, tells us about the Raising Horizons project and how their team is trying to shine the spotlight on the forgotten historical women of archaeological, geological, and palaeontological science. And Kristina Killgrove, assistant professor of anthropology at the University of West Florida and science writer, talks about the public perception of the fields of anthropology and archeology, and how those science are represented -...