Health News

Endotoxin shock protector

The bacterial toxin lipopolysaccharide (LPS) is one of the most potent virulence factors of Gram-negative bacteria that cause sepsis. Exposure to even tiny amounts can trigger a systemic—and potentially lethal—inflammatory response known as endotoxin shock.

Proinflammatory SRTFs (stress-responsive transcription factors) and lipid-regulating SREBPs (sterol regulatory element binding proteins) drive nuclear signaling pathways that have been implicated in lethal endotoxin shock. SRTFs are ferried to the cell’s nucleus by the adaptor protein importin alpha 5, whereas SREBPs are transported by importin beta 1.

Using a novel cell-penetrating peptide they designed and tested in mice that selectively suppresses nuclear transport through importin alpha 5, Jacek Hawiger, MD, Ph.D., Jozef Zienkiewicz, Ph.D., Yan Liu, MD, and colleagues showed that endotoxin shock is mediated by proinflammatory SRTFs rather than lipid-regulating SREBPs.

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