IL-1alpha in acetaminophen toxicity: a sterile danger signal
Graduate School of Biomedical Sciences, Translational Science Program; Department of Medicine, Division of Gastroenterology; UMass Metabolic Network
Letter to the Editor
Biochemistry | Cell Biology | Cellular and Molecular Physiology | Immunopathology | Molecular Biology
Much controversy surrounds the pathogenesis of acetaminophen-induced inflammation. Acetaminophen (APAP) is a well-studied xenobiotic that in high doses results in a deadly, yet preventable, form of liver failure. Although its effects are sudden and often irreversible, its mechanism is far from simple. In fact, at first glance, recent studies seem to refute each other. The field has been grappling with seemingly contradictory results driven mainly by often-generalized assumptions and different experimental systems. As always, the devil—or in this case, liver failure—is in the details. In this paper, Tang and colleagues identified macrophage-derived interleukin (IL)-1α as a mediator of sterile inflammation in a mouse model of APAP hepatotoxicity. IL-1α is an alarmin that unlike IL-1β, is constitutively expressed in many cells as a precursor. IL-1α precursor (pre-IL-1α) is active as a damage-associated molecular pattern (DAMP). After enzymatic cleavage, mature IL-1α can signal a more potent pro-inflammatory message.
DOI of Published Version
Cell Mol Immunol. 2017 Nov 20. pii: cmi2017108. doi: 10.1038/cmi.2017.108. Link to article on publisher's site
Cellular and molecular immunology
Iracheta-Vellve, Arvin and Szabo, Gyongyi, "IL-1alpha in acetaminophen toxicity: a sterile danger signal" (2017). UMass Metabolic Network Publications. 139.