Environmental Factor – March 2020: Asthma exacerbates when signaling pathway is turned on

In addition to allowing humans and animals to breathe, the lungs also play a role in the immune response and are strongly influenced by external conditions. The lungs are constantly exposed to the environment and are susceptible to inflammatory diseases, such as asthma, that are affected by substances in the air.

Garantziotis said the results confirmed the research group’s hypothesis. (Photo courtesy of Steve McCaw)

In two newly published papers, a team led by NIEHS scientists describes how environmental exposure increases and exacerbates asthma. The mechanism involves the immune pathway of a protein called Toll-like receptor 5 (TLR5). More than 26 million Americans suffer from asthma, so the findings may have important implications for alleviating the disease.

buddy leaves

Stavros Garantziotis, MD, medical director of the NIEHS Clinical Research Unit (CRU) and chair of the Matrix Biology Group, is the corresponding author for both articles. He said the first paper published in Elevi Jan 28, Describe the mechanism of TLR5. The researchers used an NIEHS-funded study group of healthy individuals (see upper sidebar) who were exposed to ozone concentrations similar to air quality index Orange or red alert level.

The participants’ lungs responded by inducing inflammation in the airway, but the study found that individuals who lacked a functional TLR5 receptor had significantly less pneumonia.

Team members found a similar result when they found blood cells from NIEHS participants Environmental polymorphism record (EPR), a North Carolina DNA bank used to find environmental determinants of human disease, was exposed to a common bacterial ingredient called endotoxin.

The second paper, published in lung On February 14, he went one step further and concluded that the TLR5 pathway activator is not only found in pollutants, but also in homes. The researchers examined EPR participants with asthma but not healthy individuals. They note that those with a nonfunctional TLR5 have fewer asthma symptoms. The team also confirmed in a mouse study that TLR5 activation promotes exacerbation of asthma.

“The papers show that TLR5 not only supports endotoxin detection by TLR4, but the results also have a much broader role in physiology as a detector for tissue damage from non-infectious environmental stress,” Wessler said. (Photo courtesy of Steve McCaw)

“We’re in a position where we can really understand the mechanisms that lead to human diseases like asthma,” Garantziotis said. “We now know what causes it to activate, what it leads to, and how we can intervene to make it less active.”

NIEHS groups work together

Michael Wessler, chief of the NIEHS Laboratory of Immunology, Infections and Diseases, worked with Garantziotis on the Elife paper. Donald Cook, PhD, chair of the immunogenetics group, did a lot of work for Lung’s article (see sidebar).

EPR was helpful in both papers. The registry contains health and exposure information for thousands of participants.

Janet Hall, Director of the National Institute for Occupational Health and Safety (NIEHS), has recognized her research importance to the NIEHS. “This resource is poised to play an increasingly important scientific role as we seek to understand the ways in which genes and the environment interact in human health,” Hall said.

Environmental Precision Medicine

The leaves have two effects, Garantiziotis said. The first is personalized medicine. Scientists can ask about exposures in a person’s home and environment that can make a person sicker and what the biology of that person makes more or less susceptible to infection. In the absence of a functional TLR5, a person is less likely to develop asthma. By default, if a person has a career prospect, they will be more vulnerable to these exposures.

“These new findings extend previous work by showing that the whip component of house dust is likely to contribute to the outbreak of asthma attacks, known as exacerbations,” Cook said. (Photo courtesy of Steve McCaw)

Second, the results may indicate environmental mitigation steps. If a TLR5 activator is in someone’s home, it makes them more likely to develop asthma. If the stimulant is removed, the asthma may become less active. It’s a genetic perspective that translates into positive health outcomes in real life.

quotes:
Hussain S, Johnson CG, Ciorba J, Meng X, Stober VP, Liu C, Cyber ​​Daily GM, Bulik K, Qian W, Solis A, Sakamachi Y, Trimbos CS, Allure GJ, Judy KM, Foster W M, Hollingsworth JW, Tighe RM, Li X, Fessler MB, Garantziotis S. 2020. TLR5 participates in the TLR4 receptor complex and enhances MyD88-dependent signaling in environmental lung injury. Elvi. doi: 10.7554/eLife.50458 [Online 28 January 2020].

Whitehead GS, Hussain S, Fannin R, Trempus CS, Innes CL, Schurman SH, Cook DN, Garantziotis S. 2020. TLR5 activation exacerbates airway inflammation in asthma. lung; doi: 10.1007/s00408-020-00337-2 [Online 14 February 2020].

The graphic shows how the two papers fit together. First, the researchers discovered the mechanism of TLR5 signaling, which is expressed by gears and DNA in the cell. Next, they worked out the effects in an animal model and then on humans after exposure to ozone and then endotoxin. Then they changed the study scenario to house dust where asthmatics were exposed like the population. This process shows how genes and the environment together influence human disease. (Photo courtesy of Stavros Garantziotis)

from San Jose News Bulletin https://sjnewsbulletin.com/environmental-factor-march-2020-asthma-exacerbates-when-signaling-pathway-is-turned-on/