Navigation Links
Pitt team finds immunity protein that ramps up inflammation, and agents that can block it
Date:3/31/2013

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.


'/>"/>

Contact: Chuck Finder
FinderCE@upmc.edu
412-996-5852
University of Pittsburgh Schools of the Health Sciences
Source:Eurekalert

Related biology news :

1. MIT research: Study finds room to store CO2 underground
2. Study finds circle hooks lower catch rate for offshore anglers
3. LSUHSC research finds HPV-related head & neck cancers rising, highest in middle-aged white men
4. Head and body lice appear to be the same species, genetic study finds
5. Study finds peoples niceness may reside in their genes
6. Large international study finds memory in adults impacted by versions of 4 genes
7. Improved loblolly pines better for the environment, study finds
8. NIST/UMass study finds evidence nanoparticles may increase plant DNA damage
9. As deadly cat disease spreads nationally, MU veterinarian finds effective treatment
10. Study finds cancer-fighting goodness in cholesterol
11. Study finds soda consumption increases overall stroke risk
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/16/2017)... Feb. 16, 2017  Genos, a community for ... it has received Laboratory Accreditation from the College ... presented to laboratories that meet stringent requirements around ... rigorous processes. "Genos is committed to ... practices. We,re honored to be receiving CAP accreditation," ...
(Date:2/10/2017)... 2017 Research and Markets has ... Medicine - Scientific and Commercial Aspects" to their offering. ... ... integrated with therapy for selection of treatment as well for ... prevention of disease in modern medicine. Biochip/microarray technologies and next ...
(Date:2/8/2017)... Report Highlights ... The global synthetic-biology market reached nearly $3.9 ... growing at a compound annual growth rate (CAGR) of 24.0% ... global markets for synthetic biology. - Analyses of global market ... of compound annual growth rates (CAGRs) through 2021. - Coverage ...
Breaking Biology News(10 mins):
(Date:2/24/2017)... Malden, MA (PRWEB) , ... February 24, 2017 ... ... disc replacement (TDR) procedures can be safely completed in an ambulatory surgery center ... and fusion (ACDF) procedures and previous two-year TDR studies. , Jake Lubinski, ...
(Date:2/24/2017)... 2017 Provectus Biopharmaceuticals, Inc. (OTCQB: PVCT, ... clinical-stage oncology and dermatology biopharmaceutical company, today is ... in its previously announced rights offering of up ... common stock and Series C Convertible Preferred Stock ... As previously announced, the rights ...
(Date:2/24/2017)...  Driven by consumers, preference towards more natural ... growing categories, finds the recently published U.S. volume ... Multi-regional Market Analysis and Opportunities study by ... "Biotechnology actives are derived from natural ... for skin and hair care applications," explains ...
(Date:2/24/2017)... Feb. 23, 2017 China Biologic Products, Inc. (NASDAQ: ... plasma-based biopharmaceutical company in China, today announced its financial results ... Fourth Quarter 2016 Financial Highlights ... by 21.7% in RMB terms, or increased by 13.6% in ... same quarter of 2015. Gross profit increased ...
Breaking Biology Technology: