Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New Signaling Role for Key Protein May Contribute to Wound Healing, Tumor Growth and Inflammatory Diseases

05.12.2014

New Signaling Role for Key Protein May Contribute to Wound Healing, Tumor Growth and Inflammatory Diseases

A key protein may represent a new way to use the immune system to speed healing and counter inflammatory, infectious and autoimmune diseases, according to study led by researchers at the Icahn School of Medicine at Mount Sinai and published in the December issue of Cell Reports.

The current study results revolve around proteinases, enzymes that break down proteins as part of cellular life. Matrix metalloproteinases or MMPs specifically target the extracellular matrix, the non-cell, structural framework within tissues.

Beyond that role, the new study found that one member of this family, MMP-2, has another signaling role related to the human immune system. It may shift a set of cells to become part of immune response that accelerates healing in some cases, but may worsen inflammatory disease in others.

Drug designers may be able to leverage the newfound MM-2 mechanisms to prevent the contribution of inflammatory signals to tumor growth and autoimmune diseases, or to promote wound healing.

“Our results show that MMP-2 uses a multitude of mechanisms to modulate the immune system,” says the study’s lead investigator Nina Bhardwaj, MD, PhD, Director of Immunotherapy, Tisch Cancer Center at Mount Sinai, Professor of Medicine, Hematology and Oncology, Icahn School of Medicine at Mount Sinai. “These data provides context to how this mechanism happens and could lead to novel treatments.”

The backdrop for the study finding is the body’s initial, vague reaction to any invading organism expands into a precise and massive counterattack. That expansion starts when a dendritic cell “swallows” a piece of any invader encountered, ferries it to the nearest lymph node and presents it there for notice by lymphocytes (B cells and T cells), the workhorses of the immune system.

DCs exposed to MMP-2 send signals that change gene expression such that more of a protein called OX40L is made, according to the study authors. OX40L is a signaling protein that links into a receptor protein on the surface of dendritic cells, like a key fitting into a lock, with their interaction changing the shape of the receptor such that other signals get sent. Among these is one that causes more immune cells within a certain part of the immune system, TH2 cells, to be made.

Though vital to effective immune responses to worms, Th2 cells have a dark side, in some cases triggering B cells to produce antibodies that recognize the body’s own cells as foreign and that destroy the kidneys of lupus patients and the joints of patients with rheumatoid arthritis. Shifting T cells in the Th2 path generally encourages inflammation.

If MMP-2 signaling leads to the presence of more Th2 T cells, it means Th2 cells will secrete more inflammatory TH2 cytokines like TNF-alpha, and interleukins 4 and 13, which fight parasite infections, but that can also contribute to autoimmune diseases if present in too large amounts. MMP-2 is also over-expressed in tumors, where it promotes cancer progression. This may in part be due to its ability to skew T cells toward Th2 differentiation, a process called type-2 polarization.

Th2 cells also contribute to wound healing because they produce cytokines, which fight infection and ultimately repair tissue. The tissue repair functions of MMP-2‘s may be due to the ability to drive Th2 immune response.

“MMP-2-mediated signaling either through direct injection or through mimics could promote wound healing but these proposed functions will require further investigation in disease-specific models,” says Dr. Bhardwaj. “Further discovery of new MMP-2 functions could lead to new reagents of inflammatory responses.”

The work was supported by a research grant from the National Institute of Health and a CLIP Award from the Cancer Research Institute. Researchers from Rockefeller University, Stanford University, New York University, Emory University and the Institut National de la Sante et de la Recherhe Medicale (INSERM) in Paris contributed to the study.

About the Mount Sinai Health System
The Mount Sinai Health System is an integrated health system committed to providing distinguished care, conducting transformative research, and advancing biomedical education. Structured around seven member hospital campuses and a single medical school, the Health System has an extensive ambulatory network and a range of inpatient and outpatient services—from community‐based facilities to tertiary and quaternary care.

The System includes approximately 6,600 primary and specialty care physicians, 12‐minority‐owned free‐standing ambulatory surgery centers, over 45 ambulatory practices throughout the five boroughs of New York City, Westchester, and Long Island, as well as 31 affiliated community health centers. Physicians are affiliated with the Icahn School of Medicine at Mount Sinai, which is ranked among the top 20 medical schools both in National Institutes of Health funding and by U.S. News & World Report.

For more information, visit http://www.mountsinai.org , or find Mount Sinai on Facebook, Twitter and YouTube.

Press Office | newswise

More articles from Life Sciences:

nachricht Symbiotic bacteria: from hitchhiker to beetle bodyguard
28.04.2017 | Johannes Gutenberg-Universität Mainz

nachricht Nose2Brain – Better Therapy for Multiple Sclerosis
28.04.2017 | Fraunhofer-Institut für Grenzflächen- und Bioverfahrenstechnik IGB

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Fighting drug resistant tuberculosis – InfectoGnostics meets MYCO-NET² partners in Peru

28.04.2017 | Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

 
Latest News

Wireless power can drive tiny electronic devices in the GI tract

28.04.2017 | Medical Engineering

Ice cave in Transylvania yields window into region's past

28.04.2017 | Earth Sciences

Nose2Brain – Better Therapy for Multiple Sclerosis

28.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>