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:

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 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


A Cure for Asthma?: What Your Doctor Isn't Telling You--and Why by David L. Hahn MD MS (2013) Paperback
by David L. Hahn MD MS (Author)

This book challenges conventional wisdom about the causes and treatments of asthma. Could hard-to-treat asthma be triggered by a persistent infection? Dr. David Hahn presents the scientific evidence and compelling case histories that led him to his surprising conclusion. He describes the treatment protocol he has used successfully. Find out if your asthma might be cured once and for all instead of managed. 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


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


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... View Details


ABC of Asthma, Allergies and Lupus: Eradicate Asthma - Now!
by F. Batmanghelidj (Author)

Breakthrough scientific information uncovers the real cause of asthma, allergies and lupus. It reveals the way to treat these conditions naturally, simply and at no cost -- initial steps towards asthma eradication.
-- Astonishingly simple guidebook for the nation's 17 million asthmatics -- 14 million of them innocent children and the 50 million who suffer from allergies.
-- Why Asthma, Allergies and Lupus are actually your body's way of alerting you to an urgent need for water... and how to recognize your body's true thirst signals.
-- In-Depth Answers to your most frequently-asked... View Details


Yoga Beats Asthma: Simple exercises and breathing techniques to relieve asthma and respiratory disorders
by Stella Weller (Author)

A comprehensive and fully accessible guide to understanding and managing asthma through yoga, encouraging sufferers away from exclusive reliance on drugs in favour of using the ancient wisdom of yoga to control the condition themselves through the powers of breathing and of the mind.

The number of asthma sufferers has risen sharply since the mid 1980s, with 10 million sufferers in the US and 3.7 million in the UK. Although many people are able to control their condition with drugs, it is still a serious condition- every six hours somebody dies from asthma in the UK.

In Yoga... View Details


Asthma Cure: Become Asthma free Now
by Common Sense Publishers

Asthma Cure describes how I cured my own asthma and the asthma treatment plan I developed through observation. The intention is that other asthma sufferers will gain hope that they do not have to be destined for a life with asthma and seek out ways to cure it and be asthma free or even apply my own method to their own situation.I did this without asthma remedies and solved asthma naturally. There are natural medications available for solving asthma naturally and some are mentioned in this book. Become asthma free now with my own methodology or adapt it to your own circumstances and perhaps... 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

Inspire To Action
What motivates us to take up a cause, follow a leader, or create change? This hour, TED speakers explore stories of inspirational leadership, and what makes some movements more successful than others. Guests include high school history teacher Diane Wolk-Rogers, writer and behavioral researcher Simon Sinek, 2016 Icelandic presidential candidate Halla Tómasdóttir, professor of leadership Jochen Menges, and writer and activist Naomi Klein.
Now Playing: Science for the People

#474 Appearance Matters
This week we talk about appearance, bodies, and body image. Why does what we look like affect our headspace so much? And how do we even begin to research a topic as personal and subjective as body image? To try and find out, we speak with some of the researchers at the Centre for Appearance Research (CAR) at the University of the West of England in Bristol. Psychology Professor Phillippa Diedrichs walks us through body image research, what we know so far, and how we know what we know. Professor of Appearance and Health Psychology Diana Harcourt talks about visible...