(Press-News.org) Scientists at the University of Pittsburgh School of Medicine have discovered a new biological pathway of innate immunity that ramps up inflammation and then identified agents that can block it, leading to increased survival and improved lung function in animal models of pneumonia. They reported their findings today in Nature Immunology.
Pneumonia and other infections sometimes provoke an inflammatory response from the body that is more detrimental than the disease-causing bacteria, said senior author Rama Mallampalli, M.D, professor and vice chair for research, Department of Medicine, and director of the Acute Lung Injury Center of Excellence at Pitt.
"In our ongoing studies of pneumonia, we found infecting bacteria activate a previously unknown protein called Fbxo3 to form a complex that degrades another protein called Fbxl2, which is needed to suppress the inflammatory response," said Dr. Mallampalli, who is also chief of the pulmonary division of the VA Pittsburgh Healthcare System. "The result is an exaggerated inflammatory response that can lead to further damage of the lung tissue, multi-organ failure and shock."
The research team, led by Bill B. Chen, Ph.D., associate professor, Division of Pulmonary, Allergy and Critical Care Medicine, conducted experiments in which mice that lacked the ability to make Fbxo3 were infected with a strain of Pseudomonas bacteria, and found that they had better lung mechanics and longer survival than mice that still made the protein.
Research team members Bryan J. McVerry, M.D., and Yingze Zhang, Ph.D., both of the Acute Lung Injury Center of Excellence, found that blood samples from 16 people who had sepsis, a condition of systemic inflammation, revealed higher levels of Fbxo3 and other inflammatory proteins and lower levels of Fbxl2 than samples from seven patients who did not have sepsis or lung infection.
Based on the structure of Fbxo3, the researchers developed a family of small molecules with the aim of inhibiting its activity. Administration of one of them, called BC-1215, led to reduced inflammatory markers and improved lung mechanics in mouse models of pneumonia and sepsis.
"The key is to find ways to help the body temper its inflammatory response so that it's able to kill the infectious agent without causing injury to healthy tissue," Dr. Mallampalli said.
"The F-box protein Fbxo3, and other related proteins, represent ideal targets for treatment of acute lung injury, because it controls the innate immune response, is upstream of important inflammatory signaling pathways, and is more selective than traditional drugs that regulate protein turnover," noted Mark T. Gladwin, M.D., chief of the Division of Pulmonary, Allergy and Critical Care Medicine, Pitt School of Medicine.
The team is beginning to study the effects of BC-125 on other conditions of systemic inflammation, such as colitis and arthritis.
###
Co-authors of the paper include Tiffany A. Coon, Jennifer R. Glasser, Jing Zhao, Ph.D., Yutong Zhao, M.D, Ph.D., Chunbin Zou, Ph.D, Bryon Ellis, and Frank C. Sciurba, M.D., all of the Acute Lung Injury Center of Excellence, University of Pittsburgh.
The study was funded by the U.S. Department of Veterans Affairs; National Institutes of Health grants HL096376, HL097376, HL098174, HL116472, HL01916, and P50HL084948; and the American Heart Association.
About the University of Pittsburgh School of Medicine
As one of the nation's leading academic centers for biomedical research, the University of Pittsburgh School of Medicine integrates advanced technology with basic science across a broad range of disciplines in a continuous quest to harness the power of new knowledge and improve the human condition. Driven mainly by the School of Medicine and its affiliates, Pitt has ranked among the top 10 recipients of funding from the National Institutes of Health since 1998. In rankings recently released by the National Science Foundation, Pitt ranked fifth among all American universities in total federal science and engineering research and development support.
Likewise, the School of Medicine is equally committed to advancing the quality and strength of its medical and graduate education programs, for which it is recognized as an innovative leader, and to training highly skilled, compassionate clinicians and creative scientists well-equipped to engage in world-class research. The School of Medicine is the academic partner of UPMC, which has collaborated with the University to raise the standard of medical excellence in Pittsburgh and to position health care as a driving force behind the region's economy. For more information about the School of Medicine, see http://www.medschool.pitt.edu.
Pitt team finds immunity protein that ramps up inflammation, and agents that can block it
Could improve treatments for pneumonia and other inflammatory conditions
2013-04-01
ELSE PRESS RELEASES FROM THIS DATE:
Is guided self-help effective in treating childhood obesity?
2013-04-01
It is known that family-based treatment that combines nutrition and exercise education, along with behavior modification, is a good approach to help children lose weight. But clinic-based weight-control programs for childhood obesity are not accessible to many families, due to issues such as cost or time commitment.
Initial studies at the University of California, San Diego School of Medicine indicate that a self-help treatment program for overweight children and their parents, guided by clinical experts, may be an effective solution. The study, led by Kerri Boutelle, ...
Varicella vaccine has long-term effectiveness against chicken pox
2013-04-01
OAKLAND, Calif., April 1, 2013 – Chicken pox, the childhood affliction of earlier generations, has been largely neutralized by the varicella vaccine, according to a new study by the Kaiser Permanente Vaccine Study Center, which appears in the current online issue of Pediatrics.
The 14-year study followed 7,585 children who were vaccinated in 1995, when they were 12 to 23 months old, to assess the long-term effectiveness of the vaccine and the impact on the epidemiology of varicella (chicken pox) and herpes zoster (shingles). Researchers also observed the impact of the ...
New technique shows promise in restoring near vision without glasses
2013-04-01
Philadelphia, Pa. (April 1, 2013) - By middle age, most people have age-related declines in near vision (presbyopia) requiring bifocals or reading glasses. An emerging technique called hyperopic orthokeratology (OK) may provide a new alternative for restoring near vision without the need for glasses, according to a study, "Refractive Changes from Hyperopic Orthokeratology Monovision in Presbyopes", appearing in the April issue of Optometry and Vision Science, official journal of the American Academy of Optometry. The journal is published by Lippincott Williams & Wilkins ...
Jogging Stroller Reviews
2013-04-01
Every month, tens of thousands of people are searching for jogging stroller reviews online. Unfortunately, only a handful of websites currently provide legitimate reviews, making it difficult for athletic parents to find unbiased information.
"It's a shame; it's hard for athletic parents to find information about jogging strollers. You never know whether you're going to make the right choice when it comes to safety and reliability" says Henry Stinson, one of the staff members at the newly launched website, BestJoggingStrollerReviews.org
The site provides ...
Geranium Street Floral: Decorate with Artificial Plants and Flowers
2013-04-01
Geranium Street Floral says plants and flowers give a very different feel to any environment: they can add vitality and color to a room that otherwise would be cold, or add serenity to a busy environment, such as a doctor's office waiting room.
Bob Smith, general manager of San Marcos, CA-based Geranium Street Floral, says artificial flowers or plants can be placed in key locations, such as a coffee table, a corner of the room or in the eaves of a window, to really add atmosphere.
Artificial plants can add an elegant and sophisticated air to a space without creating ...
The Importance of Background Checks
2013-04-01
Research conducted by the Society for Human Resource Management shows that 50% of all resumes and applications contain false information. The U.S. Department of Commerce identifies employee theft as the cause of 33% of all business failures. The Department of Justice claims workplace violence accounts for 18% of all violent crimes. 66% of negligent hiring trial cases result in jury awards averaging $600,000 in damages. Can your business afford to skip important, yet inexpensive steps such as background checks which could save time, money and headaches when it comes to hiring?
Statistics ...
GreeningtheInn Launches New and Improved Green Catalogue
2013-04-01
GreeningtheInn's target audience of green-minded hoteliers and consumers will find a more user-friendly version of their signature "Green Catalogue," launched Friday, March 28. Both the visual design and search function have been improved to provide users with easier functionality.
Companies wishing to list their product(s) in the Green Catalogue have three options available to them, including a basic free listing or upgrades to premium or featured listings. For more information on the Green Catalog, visitors can go to http://www.greeningtheinn.com, click ...
Dr. Jennifer Thompson and Dr. T. Payson Thompson join Avance Care Morrisville
2013-04-01
Dr. Pratik Desai, MD FACC, President of Avance Care, P.A. announced that Dr. Jennifer Thompson and Dr. Payson Thompson will join the team of medical professionals at Avance Care Morrisville, located at 6402 McCrimmon Parkway, Suite 100.
Dr. Jennifer Thompson, a Board Certified Family Physician, is originally from Buffalo NY and relocated to Raleigh in 1997. Dr. Thompson received her undergraduate training from SUNY Buffalo and UNC Chapel Hill, and then attended the Brody School of Medicine at East Carolina University. She comes to Avance Care with experience gained ...
Creative Performance Inc. Announces Workamajig Project Management University
2013-04-01
This content, normally reserved exclusively to our Workamajig Deployment and Workamajig Re-deployment consulting solutions, is now available to general audiences for the very first time.
Of the numerous Project Management seminars on the market, few are focused specifically on the unique needs for advertising and marketing Agency Project Managers, and none are Workamajig specific - except for ours. To be held in Portland, Oregon from May 21 to May 24, 2013, this Project Management seminar will focus on agency best practices and ways to utilize the many benefits of Workamajig ...
Bentgo, The Solution To The Common Lunch Box, Is Released
2013-04-01
The release of Bentgo, the modern all-in-one stackable lunch box, was announced today. This announcement comes at the heels of almost a year of research, development and product testing.
BPA free, FDA approved and accompanied with a 2 year warranty from date of purchase, Bentgo is a reusable, highly durable and affordable solution to the common lunch box. Each lunch style unit includes two stackable containers with lids, built-in plastic silverware and a secure strap for easy transportation. Made up of a strong plastic form that is microwave, dishwasher and freezer ...
LAST 30 PRESS RELEASES:
QUT scientists create material to turn waste heat into clean power
Major new report sets out how to tackle the ‘profound and lasting impact’ of COVID-19 on cardiovascular health
Cosmic crime scene: White dwarf found devouring Pluto-like icy world
Major report tackles Covid’s cardiovascular crisis head-on
A third of licensed GPs in England not working in NHS general practice
ChatGPT “thought on the fly” when put through Ancient Greek maths puzzle
Engineers uncover why tiny particles form clusters in turbulent air
GLP-1RA drugs dramatically reduce death and cardiovascular risk in psoriasis patients
Psoriasis linked to increased risk of vision-threatening eye disease, study finds
Reprogramming obesity: New drug from Italian biotech aims to treat the underlying causes of obesity
Type 2 diabetes may accelerate development of multiple chronic diseases, particularly in the early stages, UK Biobank study suggests
Resistance training may improve nerve health, slow aging process, study shows
Common and inexpensive medicine halves the risk of recurrence in patients with colorectal cancer
SwRI-built instruments to monitor, provide advanced warning of space weather events
Breakthrough advances sodium-based battery design
New targeted radiation therapy shows near-complete response in rare sarcoma patients
Does physical frailty contribute to dementia?
Soccer headers and brain health: Study finds changes within folds of the brain
Decoding plants’ language of light
UNC Greensboro study finds ticks carrying Lyme disease moving into western NC
New implant restores blood pressure balance after spinal cord injury
New York City's medical specialist advantage may be an illusion, new NYU Tandon research shows
Could a local anesthetic that doesn’t impair motor function be within reach?
1 in 8 Italian cetacean strandings show evidence of fishery interactions, with bottlenose and striped dolphins most commonly affected, according to analysis across four decades of data and more than 5
In the wild, chimpanzees likely ingest the equivalent of several alcoholic drinks every day
Warming of 2°C intensifies Arctic carbon sink but weakens Alpine sink, study finds
Bronze and Iron Age cultures in the Middle East were committed to wine production
Indian adolescents are mostly starting their periods at an earlier age than 25 years ago
Temporary medical centers in Gaza known as "Medical Points" (MPs) treat an average of 117 people daily with only about 7 staff per MP
Rates of alcohol-induced deaths among the general population nearly doubled from 1999 to 2024
[Press-News.org] Pitt team finds immunity protein that ramps up inflammation, and agents that can block itCould improve treatments for pneumonia and other inflammatory conditions