Endogenous histones function as alarmins in sterile inflammatory liver injury through Toll-like receptor 9 in mice.

ABSTRACT:

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Sterile inflammatory insults are known to activate innate immunity and propagate organ damage through the recognition of extracellular damage-associated molecular pattern (DAMP) molecules. Although DAMPs such as endogenous DNA and nuclear high-mobility group box 1 have been shown to be critical in sterile inflammation, the role of nuclear histone proteins has not yet been investigated. We report that endogenous histones function as DAMPs after ischemic injury through the pattern recognition receptor Toll-like receptor (TLR) 9 to initiate inflammation. Using an in vivo model of hepatic ischemia/reperfusion (I/R) injury, we show that levels of circulating histones are significantly higher after I/R, and that histone neutralization significantly protects against injury. Inj

SUBMITTER: Huang H 

PROVIDER: S-EPMC3213322 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature