May 9, 2018

Putting the brakes on sepsis

An enzyme called PTEN reduces inflammatory signaling and mortality in sepsis, suggesting it may be a good therapeutic target for this life-threatening complication of infection.

Sepsis — an extreme response to infection — can cause damage to multiple organ systems when it triggers an uncontrolled inflammatory response.

C. Henrique Serezani, PhD, and colleagues are seeking molecular “brakes” that will dampen sepsis-induced inflammation and prevent organ damage. They investigated a role for an enzyme called PTEN, a lipid and protein phosphatase that regulates various pathways of the immune response.

They found increased expression of the PTEN gene in white blood cells from patients and mice with sepsis, but greatly reduced levels of PTEN protein in septic patients with severe illness. The researchers showed that blocking PTEN genetically or pharmacologically increased bacterial load, inflammation, lung injury and death in mice with sepsis. They demonstrated that PTEN induces the production of microRNAs that regulate gene expression to reduce inflammatory signaling.

The findings, reported May 1 in Science Signaling, identify a previously uncharacterized role for PTEN in regulating microRNA production and decreasing the mortality and comorbidities associated with sepsis.

This research was supported by grants from the National Institutes of Health (HL103777, HL124159, AI060519, GM099773, GM108025), an American Lung Association Senior Research Training Fellowship, Coordination for the Improvement of Higher Education Personnel, and São Paulo Research Foundation (FAPESP).

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