Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Deactivating the alarm

26.04.2010
Therapeutic strategies that block inflammatory response to islet cell transplantation may accelerate treatment of diabetic patients

For patients with insulin-dependent diabetes mellitus, the only route to full recovery without daily injections of insulin is by transplantation of pancreatic islet cells. This can be achieved non-surgically via injection of donor cells into the liver, but such treatment also elicits a vigorous negative response from the body.

“Transplantation tolerance can be controlled by immunosuppressive drugs such as FK506,” says Masaru Taniguchi of the RIKEN Research Center for Allergy and Immunology in Yokohama. “However, transplanted islets are rejected soon after transplantation even with the use of FK506.” The mechanism for this rejection is unknown, and patients must typically receive several injections from multiple donors for transplantation to succeed.

High-mobility group box 1 (HMGB1) was first identified as a DNA-binding factor in the cell nucleus, but it is also secreted by immune cells as an apparent trigger for inflammation in response to tissue damage. Taniguchi’s team recently joined forces with Yohichi Yasunami at Fukuoka University to demonstrate the impact of this protein on transplanted islet survival.

They produced diabetic mice by treating the animals with an islet-killing drug, and then transplanted varying numbers of donor islet cells. Animals receiving 200 cells normally developed diabetic symptoms, but these could be averted by simultaneous treatment with HMGB1-blocking antibodies. This treatment also prevented accumulation of immune cells in the liver and countered the production of inflammatory cytokines—typical outcomes of islet transplantation.

The researchers were surprised to note that HMGB1 expression was highly specific to islet cells, with protein levels 20-fold higher than any other organ or tissue examined, further supporting its particular role in islet rejection. In fact, they noted two strong peaks in plasma levels of HMGB1 in transplant recipients: one 24 hours after chemical destruction of islets, and another 6 hours after islet injection. These results suggest that islet stress or damage directly triggers HMGB1 secretion, which in turn activates the inflammatory response pathways that initiate destruction of the transplanted cells.

These findings provide strong hope for improving transplant efficiency. “We can use antibodies in humans without any side effects, because HMGB1 is not present in the serum under physiological conditions,” says Taniguchi, who adds that Yasunami’s team is now exploring clinical strategies based on this approach. However, Taniguchi also hopes to develop chemical inhibitors that preemptively block HMGB1 secretion by donor cells prior to transplantation. “This is ideal,” he says, “because then we do not need to treat patients with any drugs or antibodies.”

The corresponding author for this highlight is based at the Laboratory for Immune Regulation, RIKEN Research Center for Allergy and Immunology

Journal information

1. Matsuoka, N., Itoh, T., Watarai, H., Sekine-Kondo, E., Nagata, N., Okamoto, K., Mera, T., Yamamoto, H., Yamada, S., Maruyama, I. et al. High-mobility group box 1 is involved in the initial events of early loss of transplanted islets in mice. The Journal of Clinical Investigation 120, 735–743 (2010).

gro-pr | Research asia research news
Further information:
http://www.riken.jp
http://www.rikenresearch.riken.jp/eng/research/6238
http://www.researchsea.com

Further reports about: Allergy Deactivating HMGB1 Immunology RIKEN immune cell immunosuppressive drug islet cells

More articles from Life Sciences:

nachricht Decoding the genome's cryptic language
27.02.2017 | University of California - San Diego

nachricht New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Safe glide at total engine failure with ELA-inside

On January 15, 2009, Chesley B. Sullenberger was celebrated world-wide: after the two engines had failed due to bird strike, he and his flight crew succeeded after a glide flight with an Airbus A320 in ditching on the Hudson River. All 155 people on board were saved.

On January 15, 2009, Chesley B. Sullenberger was celebrated world-wide: after the two engines had failed due to bird strike, he and his flight crew succeeded...

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

New pop-up strategy inspired by cuts, not folds

27.02.2017 | Materials Sciences

Sandia uses confined nanoparticles to improve hydrogen storage materials performance

27.02.2017 | Interdisciplinary Research

Decoding the genome's cryptic language

27.02.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>