A Role for MK2 in Enhancing Neutrophil-Derived ROS Production and Aggravating Liver Ischemia/Reperfusion Injury.

Increased inflammatory responses and enhanced reactive oxygen species contribute to hepatic ischemia/reperfusion (I/R) injury, however the modulatory mechanisms haven't been completely unveiled. Here, we report that genetic deficiency of MAPK-activated protein kinase 2 (MK2) protected against hepatic I/R injury and decreased hepatic neutrophil accumulation in MK2^-/- mice. Depletion of neutrophil attenuated hepatic I/R injury in wide type mice. In response to C5a stimulation, MK2^-/- neutrophils generated less superoxide in which both NADPH oxidase activation and p47^phox phosphorylation were decreased. Furthermore, Ser329 of p47^phox was identified for enhancement of superoxide production. The Ser329 phosphorylation was reduced in MK2^-/- neutrophils. To determine whether MK2 modulates hepatic I/R injury via activating neutrophils, we generated myeloid-specific MK2 deletion mice (MK2^Lyz2-KO) and liver I/R injury was reduced in MK2^Lyz2-KO mice. Our results indicate that MK2 augments hepatic I/R injury and induces production with increased p47^phox phosphorylation and MK2 is a potential drug target for treating hepatic I/R injury.

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