Deleting Enzymes Takes The Edge Off Septic Shock

Inhibiting IPMK enzymes could help dampen the overexuberant immune response during sepsis, a leading cause of death from infections.

AsianScientist (May 16, 2017) – Researchers from the Korea Advanced Institute of Science and Technology (KAIST) have identified an important enzyme that plays a key role in the response to septic shock in mice. Their findings, published in Science Advances, could help make sepsis less deadly.

The enzyme, called inositol polyphosphate multikinase (IPMK) is essential for the biosynthesis of the sugar inositol. In addition, IPMK has been found to control cellular growth and energy homeostasis. In the present study, first author PhD candidate Kim Eunha has shown that the deletion of IPMK in macrophages could significantly reduce levels of inflammation and increase the survival rates of mice challenged with septic shock and endotoxins.

The team further discovered that IPMK enzymes directly bind to TRAF6 proteins, a key player in immune signaling, thus protecting TRAF6 proteins from ubiquitination reactions that are involved in protein degradation. In addition, Kim and his colleagues successfully verified this IPMK-dependent immune control by employing short peptides which can specifically interfere with the binding between IPMK enzymes and TRAF6 proteins in macrophage cells.

This research revealed a novel function of IPMK enzymes in the fine tuning of innate immune signaling networks, suggesting a new direction for developing therapeutics targeting serious medical conditions such as neuroinflammation, type 2 diabetes, as well as polymicrobial sepsis that are developed from uncontrolled host immune responses.

The article can be found at: Kim et al. (2017) Inositol Polyphosphate Multikinase Promotes Toll-like Receptor–induced Inflammation by Stabilizing TRAF6.


Source: Korea Advanced Institute of Science and Technology.
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