Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Novel research lays the groundwork for new therapies against sepsis

11.04.2016

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!

More articles from Health and Medicine:

nachricht Tracking movement of immune cells identifies key first steps in inflammatory arthritis
23.01.2017 | Massachusetts General Hospital

nachricht Team discovers how bacteria exploit a chink in the body's armor
20.01.2017 | University of Illinois at Urbana-Champaign

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Quantum optical sensor for the first time tested in space – with a laser system from Berlin

For the first time ever, a cloud of ultra-cold atoms has been successfully created in space on board of a sounding rocket. The MAIUS mission demonstrates that quantum optical sensors can be operated even in harsh environments like space – a prerequi-site for finding answers to the most challenging questions of fundamental physics and an important innovation driver for everyday applications.

According to Albert Einstein's Equivalence Principle, all bodies are accelerated at the same rate by the Earth's gravity, regardless of their properties. This...

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Tracking movement of immune cells identifies key first steps in inflammatory arthritis

23.01.2017 | Health and Medicine

Electrocatalysis can advance green transition

23.01.2017 | Physics and Astronomy

New technology for mass-production of complex molded composite components

23.01.2017 | Process Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>