DAMPs ramp up drug toxicity.
The clinical syndrome of acetaminophen-induced liver injury represents the combined result of drug toxicity and a potent innate immune response that follows drug-induced cell death. In this issue of the JCI, Imaeda and colleagues report that DNA released from dying hepatocytes is a key stimulus of innate immune activation in the acetaminophen-treated mouse liver (see the related article beginning on page 305). They present evidence indicating that hepatocyte DNA promotes immune activation by acting as a danger-associated molecular pattern (DAMP) that stimulates cytokine production in neighboring sinusoidal endothelial cells via Tlr9 and the Nalp3 inflammasome.
Maher
Jacquelyn J
JJ
Department of Medicine and Liver Center, UCSF, San Francisco, California, USA. jmaher@medsfgh.ucsf.edu
D000082:Acetaminophen / Q000633:toxicity*; D018712:Analgesics, Non-Narcotic / Q000633:toxicity*; D000818:Animals; D007113:Immunity, Innate; D007249:Inflammation / Q000209:etiology*; D008099:Liver / Q000187:drug effects*; D051379:Mice; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000502:physiology*
D018712:Analgesics, Non-Narcotic; D051193:Toll-Like Receptors; D000082:Acetaminophen