Protective role for SHARPIN, a protein involved in regulating inflammation, according to report in The American Journal of Pathology
Sepsis represents a serious complication of infection and is one of the leading causes of death and critical illness worldwide due in part to the lack of effective therapies.
Confocal images of human monocytes immunostained with antibodies toward SHARPIN (red) and caspase 1 (green). Notice the dramatic increase in caspase 1 upon stimulation with lipopolysaccharide (LPS) and ATP, and its co-localization with SHARPIN as visualized by the merged fluorescence (yellow). Nuclei are stained blue with DAPI.
Credit: The American Journal of Pathology
A report in the American Journal of Pathology provides evidence from both mouse and human studies that SHARPIN, a protein involved in regulating inflammation, has anti-septic effects. These findings may spur development of novel sepsis treatments.
"Sepsis has been linked to enhanced activity of the enzyme caspase 1 and aberrant expression of pro-inflammatory interleukins 1β and 18. SHARPIN binds to caspase 1 and inhibits its activation.
Our study proposes that the caspase 1/SHARPIN interaction may be a key pharmacological target in sepsis and, perhaps, in other inflammatory conditions where SHARPIN is involved," explained Liliana Schaefer, MD, Professor of Pharmacology at the Institut fur Allgemeine Pharmakologie und Toxikologie of the Klinikum der Goethe-Universität Frankfurt am Main (Germany).
The investigators found that sepsis in mice bred to be deficient in SHARPIN resulted in enhanced levels of interleukins 1β and 18 and active caspase 1, as well as shortened survival. Treatment with a caspase 1 inhibitor reversed these effects by reducing levels of interleukins 1β and 18, decreasing cell death in the spleen, and prolonging survival.
The investigators also reported for the first time that this mechanism may be relevant to human sepsis. "We found a decline in SHARPIN levels in septic patients correlating with enhanced activation of caspase 1 in circulating mononuclear cells and an increase of interleukin1β/18 in the plasma," noted Dr. Schaefer.
"Our findings suggest that using pharmacological caspase 1 inhibitors could be beneficial in septic patients with low SHARPIN levels and these therapies may be more efficient than other anti-inflammatory therapies."
A recent Task Force convened by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine (JAMA 2016;315:801) define sepsis as "a life-threatening organ dysfunction caused by a dysregulated host response to infection."
Septic shock comprises a subset of sepsis in which underlying circulatory and cellular metabolism abnormalities are severe enough to substantially increase the risk of death. Symptoms of sepsis include changes in body temperature, rapid heart rate, and rapid breathing. Other indicators are reduced urine output, changes in mental status, breathing difficulty, abdominal pain, and low platelet count.
Eileen Leahy | EurekAlert!
23.03.2017 | Technische Universität München
How prenatal maternal infections may affect genetic factors in Autism spectrum disorder
22.03.2017 | University of California - San Diego
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
23.03.2017 | Life Sciences
23.03.2017 | Power and Electrical Engineering
23.03.2017 | Earth Sciences