New findings on ‘key players’ in brain inflammation
Inflammation is a natural reaction of the body’s immune system to an aggressor or an injury, but if the inflammatory response is too strong it becomes harmful. Inflammatory processes occur in the brain in conjunction with stroke and neurological diseases such as Alzheimer’s and Parkinson’s disease. Researchers from Lund University and Karolinska Institutet in close collaboration with University of Seville have presented new findings about some of the ‘key players’ in inflammation. In the long term, these findings could lead to new treatments.
One of these key players is a receptor called TLR4. The receptor plays such an important role in the body’s innate immune system that the researchers who discovered it were awarded the 2011 Nobel Prize in Physiology or Medicine. The other key player is a protein called galectin-3, which is absent in healthy brains but present in a brain suffering ongoing inflammation.
Researchers have now demonstrated that galectin-3 is secreted by microglial cells, a type of immune cell in the brain. The protein binds to the TLR4 receptor and amplifies the reactions that lead to inflammation. More galectin-3 is produced and binds to the immune cells, and the immune response is further intensified in a self-sustaining process.
Various different methods
The study, which is published in the journal Cell Reports, demonstrates the importance of the link between the two ‘key players’ using various different methods and in laboratory tests, animal experiments and human trials. The researchers have shown that mice genetically modified to be incapable of synthesising galectin-3 show a lower inflammatory response and less brain damage after model mimicing a heart attack. Mice with a model of Parkinson’s disease also suffer less brain damage if they do not have the gene for galectin-3. Researchers also observed the interaction between galectin-3 and TLR4 in the brains of people who died of a stroke.
First study-author Miguel Angel Burguillos is currently working at Queen Mary University of London, but carried out the work on galectin-3 and TLR4 during his time as a postdoctoral fellow at Lund University and Karolinska Institutet. The research in Lund has been led by Tomas Deierborg and at Karolinska Institutet by Bertrand Joseph. The University of Seville also participated in the research.
This work has been supported by the A.E. Berger Foundation, the Bergvall Foundation, the Crafoord Foundation, the G & J Kock Foundation, the Gyllenstiernska Krapperup Foundation, Lars Hierta Memorial Foundation, Proyecto de Excelencia from Junta de Andalucia, the Royal Physiographic Society in Lund, Spanish Ministerio de Ciencia y Tecnología, the Swedish Childhood Cancer Society, the Swedish Parkinson Foundation, the Swedish Research Council, the Swedish Strategic Research Area MultiPark at Lund University, the Swedish National Stroke Foundation, and the Wiberg foundation.
- Read more about the study on the website of Queen Mary University of London
- View a news article in Spanish on the website of University of Seville
Microglia-secreted Galectin-3 acts as a Toll-Like Receptor-4 ligand and contributes to microglial activation
Miguel Burguillos, Martina Svensson, Tim Schulte, Antonio Boza-Serrano, Albert Garcia-Quintanilla, Edel Kavanagh, Martiniano Santiago, Nikenza Viceconte, Maria Jose Oliva-Martin, Ahmed Osman, Emma Salomonsson, Lahouari Amar, Annette Persson, Klas Blomgren, Adnane Achour, Elisabet Englund, Hakon Leffler, Jose Luis Venero, Bertrand Joseph, Tomas Deierborg
Cell Report, online 5 March 2015, DOI: http://dx.doi.org/10.1016/j.celrep.2015.02.012