The study, published online ahead of print, will appear Nov. 15 in the journal Immunity. Specifically, the study reveals that two molecular pathways, the Notch and Toll-like receptor pathways, are linked and that manipulating a protein called RBP-J involved in both pathways, could serve as a treatment for rheumatoid arthritis.
"This is a basic science papers with translational and clinical implications, as it identifies a potential new therapeutic target in the treatment of inflammatory disorders," said Lionel Ivashkiv, M.D., director of Basic Research at Hospital for Special Surgery in New York City. He said that drugs, so-called gamma secretase inhibitors that hit this new target, are actually in trials for the treatment of another disease, leukemia.
Previous research has shown that activation of certain cell surface receptors called Toll-like receptors leads to the production of inflammatory proteins or cytokines. Researchers have also known that a protein called interferon gamma can increase inflammatory response, but they didn't know the exact mechanism.
To find out, they turned to microarray analysis, a method of surveying an entire genome to determine which genes are being expressed or which are responsible for a certain condition. Using this technology with human macrophages, white blood cells that are vital to the development of inflammatory response, they identified a subset of genes that were turned on by the activation of Toll-like receptors and inhibited by interferon gamma. This subset of genes included genes that are involved in the Notch signaling pathway. For some time, scientists have known that the Notch signaling pathway regulates cell differentiation, proliferation, survival and development.
"Before this study, we knew that the Notch pathway was important in development and that the Toll-like receptor pathways were important in acute inflammation, and now we know that those two things are linked in acute inflammation and cytokine production," said Dr. Ivashkiv.
When molecules dock on the Toll-like receptors of macrophages, proteins including interleukin-6, which has been implicated in rheumatoid arthritis, are produced. In another experiment, investigators showed that the production of interleukin-6 was decreased if a protein called RBP-J was not present. Investigators also found that interfering with the production of RBP-J decreased the activation of certain Notch target genes.
"The Toll-like receptors regulate the Notch pathway, but the Notch pathways also regulates the Toll-like receptors, and it all seems to be through this RBP-J protein," said Dr. Ivashkiv. He says that other studies have shown that drugs called gamma secretase inhibitors have been shown to interfere with the Notch pathway and thus could be used to treat rheumatoid arthritis by decreasing the amount of interleukin-6.
Phyllis Fisher | EurekAlert!
How cancer metastasis happens: Researchers reveal a key mechanism
19.01.2018 | Weill Cornell Medicine
Researchers identify new way to unmask melanoma cells to the immune system
17.01.2018 | Duke University Medical Center
Physicists have developed a technique based on optical microscopy that can be used to create images of atoms on the nanoscale. In particular, the new method allows the imaging of quantum dots in a semiconductor chip. Together with colleagues from the University of Bochum, scientists from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute reported the findings in the journal Nature Photonics.
Microscopes allow us to see structures that are otherwise invisible to the human eye. However, conventional optical microscopes cannot be used to image...
On the way to an intelligent laboratory, physicists from Innsbruck and Vienna present an artificial agent that autonomously designs quantum experiments. In initial experiments, the system has independently (re)discovered experimental techniques that are nowadays standard in modern quantum optical laboratories. This shows how machines could play a more creative role in research in the future.
We carry smartphones in our pockets, the streets are dotted with semi-autonomous cars, but in the research laboratory experiments are still being designed by...
What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...
For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.
Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...
At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.
No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...
08.01.2018 | Event News
11.12.2017 | Event News
08.12.2017 | Event News
23.01.2018 | Life Sciences
23.01.2018 | Earth Sciences
23.01.2018 | Physics and Astronomy