Breaking News
January 20, 2019 - New study takes first step toward treating endometriosis
January 20, 2019 - Researchers find how GREB1 gene promotes resistance to prostate cancer treatments
January 20, 2019 - Replacing Sitting Time With Activity Lowers Mortality Risk
January 20, 2019 - A simple, inexpensive intervention makes birth safer for moms and babies in parts of Africa
January 19, 2019 - New anti-inflammatory compound acts as ‘surge protector’ to reduce cancer growth
January 19, 2019 - Significant flaws found in recently released forensic software
January 19, 2019 - New Leash on Life? Staying Slim Keeps Pooches Happy, Healthy
January 19, 2019 - Men and women remember pain differently
January 19, 2019 - Rising air pollution linked with increased ER visits for breathing problems
January 19, 2019 - Study uses local data to model food consumption patterns among Seattle residents
January 19, 2019 - The brain’s cerebellum plays role in controlling reward and social behaviors, study shows
January 19, 2019 - Relationship between nurse work environment and patient safety
January 19, 2019 - Pioneering surgery restores movement to children paralyzed by acute flaccid myelitis
January 19, 2019 - Genetic variants linked with risk tolerance and risky behaviors
January 19, 2019 - New research provides better understanding of our early human ancestors
January 19, 2019 - First-ever tailored reporting guidance to improve patient care and outcomes
January 19, 2019 - 4.6 percent of Massachusetts residents have opioid use disorder
January 19, 2019 - New study suggests vital exhaustion as risk factor for dementia
January 19, 2019 - New antibiotic discovery heralds breakthrough in the fight against drug-resistant bacteria
January 19, 2019 - Ural Federal University scientists synthesize a group of multi-purpose fluorophores
January 19, 2019 - Researchers identify new therapeutic target in the fight against chronic liver diseases
January 19, 2019 - Preparation, characterization of Soyasapogenol B loaded onto functionalized MWCNTs
January 19, 2019 - FDA Approves Ontruzant (trastuzumab-dttb), a Biosimilar to Herceptin
January 19, 2019 - Tobacco use linked with higher use of opioids and sedatives
January 19, 2019 - Study delves deeper into developmental dyslexia
January 19, 2019 - Anti-vaccination movement one of the top health threats in 2019 says WHO
January 19, 2019 - Newly developed risk score more effective at identifying type 1 diabetes
January 19, 2019 - Highly effective protocol to prepare cannabis samples for THC/CBD analysis
January 19, 2019 - Prinston Pharmaceutical Inc. Issues Voluntary Nationwide Recall of Irbesartan and Irbesartan HCTZ Tablets Due to Detection of a Trace Amount of Unexpected Impurity, N-Nitrosodiethylamine (NDEA) in the Products
January 19, 2019 - How does solid stress from brain tumors cause neuronal loss, neurologic dysfunction?
January 19, 2019 - $14.7 million partnership to supercharge vaccine development
January 19, 2019 - Ian Fotheringham receives Charles Tennant Memorial Lecture award
January 19, 2019 - Brain vital signs detect neurophysiological impairments in players with concussions
January 19, 2019 - Lack of job and poor housing conditions increased likelihood of people attending A&E
January 19, 2019 - Novel targeted drug delivery system improves conventional cancer treatments
January 19, 2019 - Rutgers study finds gene responsible for spread of prostate cancer
January 19, 2019 - Complications Higher Than Expected for Invasive Lung Tests
January 19, 2019 - 3-D printed implant promotes nerve cell growth to treat spinal cord injury
January 19, 2019 - Automated texts lead to improved outcomes after total knee or hip replacement surgery
January 19, 2019 - Poor cardiorespiratory fitness could increase risk of future heart attack, finds new study
January 19, 2019 - Drinking soft drinks while exercising in hot weather may increase risk of kidney disease
January 19, 2019 - Formlabs 3D prints anatomical models
January 19, 2019 - Heart-Healthy Living Also Wards Off Type 2 Diabetes
January 19, 2019 - Teaching Kids to Be Smart About Social Media (for Parents)
January 19, 2019 - Metabolite produced by gut microbiota from pomegranates reduces inflammatory bowel disease
January 19, 2019 - Researchers examine how spray from showers and toilets expose us to disease causing bacteria
January 19, 2019 - Behavioral experiments confirm that additional neurons improve brain function
January 19, 2019 - New study compares performance of real-time infectious disease forecasting models
January 19, 2019 - Obesity can be risk factor for developing renal cell carcinoma, confirms study
January 19, 2019 - New regulation designs on cigarette packs direct smokers’ attention to health warnings
January 19, 2019 - QIAGEN receives first companion diagnostic approval in Japan
January 19, 2019 - Study explores role of Dunning-Kruger effect in anti-vaccine attitudes
January 19, 2019 - Newly identified subset of immune cells may be key to fighting chronic inflammation
January 19, 2019 - New immune response regulators discovered
January 18, 2019 - Poor blood oxygenation during sleep predicts chance of heart-related death
January 18, 2019 - First international consensus on the diagnosis and management of fibromuscular dysplasia
January 18, 2019 - Rapid resistance gene sequencing technology can hasten identification of antibiotic-resistant bacteria
January 18, 2019 - Researchers develop artificial enzymatic pathway for synthesizing isoprenoids in E. coli
January 18, 2019 - Scientists advise caution in immunotherapy research
January 18, 2019 - How children across the world develop language
January 18, 2019 - Columbia Medical Student Receives McDonogh Scholarship
January 18, 2019 - Secretive ‘Rebate Trap’ Keeps Generic Drugs For Diabetes And Other Ills Out Of Reach
January 18, 2019 - Plant based diet could be the best option for the planet says commission
January 18, 2019 - New conservation practice could reduce nitrogen from agricultural drainage, study shows
January 18, 2019 - UIC researchers receive $1.7 million NCI grant to study Southeast Asian fruit
January 18, 2019 - New study determines the fate of DNA derived from genetically modified food
January 18, 2019 - Scientists develop new gene therapy that prevents axon destruction in mice
January 18, 2019 - Study finds critically low HPV vaccination rates among younger adolescents in the U.S.
January 18, 2019 - Brain cells involved in memory play key role in reducing future eating behavior
January 18, 2019 - Risk for Conversion of MS Varies With Different Therapies
January 18, 2019 - Investigational cream may help patients with inflammatory skin disease
January 18, 2019 - Medical school news office receives six writing awards | News Center
January 18, 2019 - County By County, Researchers Link Opioid Deaths To Drugmakers’ Marketing
January 18, 2019 - Research reveals risk for developing more than one mental health disorder
January 18, 2019 - Scientists discover a dramatic pattern of bone growth in female mice
January 18, 2019 - Study finds link between lengthy periods of undisturbed maternal sleep and stillbirths
January 18, 2019 - New nuclear medicine method could improve detection of primary and metastatic melanoma
January 18, 2019 - Combination therapy shows high efficacy in treating people with leishmaniasis and HIV
January 18, 2019 - Health Tip: Don’t Ignore Changes in Skin Color
January 18, 2019 - Dietary Recommendations for Healthy Children
Researchers identify pathway to resolve allergic asthma

Researchers identify pathway to resolve allergic asthma

image_pdfDownload PDFimage_print

A group of Brazilian researchers succeeded in preventing allergic asthma from progressing in experimental models by increasing the amount of a protein. This increase, in turn, blocked the CD4+ T lymphocytes responsible for producing a cytokine that triggers a cascade of events resulting in the onset and progression of the disease.

This knowledge of how the disease can be resolved in cell cultures and animals will form a basis for the research and development of a drug to control expression of this protein in experimental models and humans.

The study was conducted by members of the Center for Research on Inflammatory Diseases (CRID), a Research, Innovation & Dissemination Center (RIDC) funded by São Paulo Research Foundation – FAPESP.

The results were published in the Journal of Allergy and Clinical Immunology and are part of a São Paulo Research Foundation – FAPESP-supported postdoctoral research project for which the grantee is Luciana Benevides, a researcher at the University of São Paulo’s Ribeirão Preto Medical School (FMRP-USP) and first author of the article.

“People with allergic or bronchial asthma are currently prescribed drugs such as antihistamines, bronchodilators, and corticosteroids, which inhibit the symptoms of the disease but also inhibit the cellular response, including that of TH2 lymphocytes,” said João Santana da Silva, a professor at FMRP and principal investigator for the project.

“TH2 lymphocytes lead to the production of substances that cause the symptoms, so this treatment strategy targets only symptoms such as rhinorrhea [runny nose], breathlessness and so on. What we discovered is that, if other T lymphocytes called TH9 cells are blocked, the disease will be effectively resolved and the production of substances that cause the symptoms will stop,” Silva said.

To achieve these results, the researchers performed experiments with cell cultures from mice and humans as well as transgenic mice.

The experiments confirmed that when the gene Blimp-1 is overexpressed, production of the protein it encodes, which is also called Blimp-1, increases, and this protein blocks the action of the lymphocytes that produce IL-9, a cytokine that causes allergic airway inflammation. “The key point is that blocking IL-9 weakens the response by TH2 cells, slowing progression of the disease,” Benevides.

Blimp-1 gene

To test the hypothesis that Blimp-1 plays an important role in allergy resolution, the researchers created transgenic mice with this gene switched off in their T lymphocytes.

Because the gene has other functions, it could not be completely silenced, so they used a technique called conditional knockout, so the gene would fail to function only in T-cells.

Next, both transgenic mice with Blimp-1 deleted in their T-cells and control mice were submitted to a procedure that induced an allergy. The researchers injected doses of ovalbumin and then introduced the same substance into the animals’ nostrils (intranasal instillation), producing airway inflammatory disease as a result of an allergy to egg white protein.

When they analyzed the reactions in the two groups of animals, they found that the mice without Blimp-1 suffered the effects of allergy much more than the mice that had the active gene.

“Although both groups developed the allergy, we showed that the animals without Blimp-1 in their T-cells had far more intense lung inflammation than the control animals,” Benevides said.

Having demonstrated the role of Blimp-1 in inflammation, the researchers created a method for overexpressing the gene to see whether the abnormally large amount of protein produced would inhibit production of the cytokine IL-9.

They then collected samples of human peripheral blood mononuclear cells, which are widely used in immunology research. Samples were collected from healthy individuals and people with allergic asthma.

The blood cells received an innocuous virus or a virus that contained Blimp-1, which became part of the cells’ DNA. In cells from both healthy and asthmatic individuals, Blimp-1 produced large amounts of protein and inhibited the production of TH9, which produces IL-9.

Although IL-9 was expressed in the cells from both healthy and asthmatic individuals, its expression was more intense in the latter. The same result was observed in a similar experiment with murine cells.

Use in other diseases

Based on these findings, the group now plans to develop drugs capable of inducing Blimp-1 expression to control TH9 cells. “We’re testing its role in the regulation of TH9 cells using other experimental models, such as tumors, but it’s too soon to draw any conclusions,” Benevides said.

In the case of cancers such as melanoma, preliminary experiments that have not yet been published show that when Blimp-1 expression is reduced, the resulting increase in TH9 cells leads to a reduction in tumor size.

A cancer drug developed on this basis would therefore inhibit Blimp-1 expression, whereas a drug for asthma and autoimmune diseases would boost Blimp-1 expression.

“The most important discovery is a new function for a well-known transcription factor, which we now know to also be capable of inhibiting the differentiation of IL-9-producing T-cells. This opens up the prospect of research on several diseases in which TH9 cells are involved,” Benevides said.

Source:

http://agencia.fapesp.br/pathway-to-resolve-allergic-asthma-is-discovered-/29115/

About author

Related Articles