Discovered a cellular process that leads to inflammation. « Medicine in the Library

The researchers of Cedars-Sinai have identified several steps in a cellular process responsible for activating one of the body’s important inflammatory responses. Their findings, published in the scientific journal Science Immunologyopen up the possibility of modulating the type of inflammation associated with different infections and inflammatory diseases.

Researchers have improved understanding of the steps leading to the production of IL-1 beta, a potent inflammatory signal protein released during many inflammatory responses.

“Inflammation, in many cases, is vital to a thriving immune system and healthy body” say the researchers. “However, prolonged inflammation can wreak havoc on the body. This underscores the importance of understanding the cellular process of how inflammation is triggered“.

“We now have a clearer understanding of the step-by-step process that leads to the production of IL-1 betasaid Andrea Wolf, PhD, assistant professor of biomedical sciences and medicine at Cedars-Sinai and senior author and correspondent on the new study. “By understanding the process, we hope one day to find a treatment for the diseases associated with this inflammatory response.”.

The researchers had previously discovered that an enzyme called hexokinase, typically used by cells to convert glucose into energy, has a second inflammatory function. They found that hexokinase binds to a sugar in the bacterial cell wall and activates inflammasomes, leading to the production of IL-1 beta.

Now they have discovered that hexokinase leaves the mitochondria, the part of a cell that generates energy. This triggers an immune response: the release of hexokinase destabilizes the mitochondria and alerts the cell that something is wrong. This leads to the assembly of a channel called VDAC in the mitochondrial membrane, which interacts with another protein called NLRP3 to initiate inflammasome assembly. Inflammasomes then produce IL-1 beta, a driver of inflammation.

Read the full text of the article:
Hexokinase dissociation from mitochondria promotes oligomerization of VDAC that facilitates NLRP3 inflammasome assembly and activation
BY SUNG HOON BAIK, V. KRISHNAN RAMANUJAN, ET AL.
SCIENCE IMMUNOLOGY 16 Jun 2023 Vol 8, Issue 84 DOI: 10.1126/sciimmunol.ade7652

Source: Biomedical Sciences and Medicine at Cedars-Sinai