| Autor: |
Bang S; Center for Translational Pain Medicine, Department of Anesthesiology, Duke University Medical Center, Durham, NC, USA., Donnelly CR; Center for Translational Pain Medicine, Department of Anesthesiology, Duke University Medical Center, Durham, NC, USA., Luo X; Center for Translational Pain Medicine, Department of Anesthesiology, Duke University Medical Center, Durham, NC, USA., Toro-Moreno M; Department of Chemistry, Duke University, Durham, NC, USA., Tao X; Center for Translational Pain Medicine, Department of Anesthesiology, Duke University Medical Center, Durham, NC, USA., Wang Z; Center for Translational Pain Medicine, Department of Anesthesiology, Duke University Medical Center, Durham, NC, USA., Chandra S; Center for Translational Pain Medicine, Department of Anesthesiology, Duke University Medical Center, Durham, NC, USA., Bortsov AV; Center for Translational Pain Medicine, Department of Anesthesiology, Duke University Medical Center, Durham, NC, USA., Derbyshire ER; Department of Chemistry, Duke University, Durham, NC, USA., Ji RR; Center for Translational Pain Medicine, Department of Anesthesiology, Duke University Medical Center, Durham, NC, USA. ru-rong.ji@duke.edu.; Department of Neurobiology, Duke University Medical Center, Durham, NC, USA. ru-rong.ji@duke.edu.; Department of Cell Biology, Duke University Medical Center, Durham, NC, USA. ru-rong.ji@duke.edu. |
| Abstrakt: |
GPR37 was discovered more than two decades ago, but its biological functions remain poorly understood. Here we report a protective role of GPR37 in multiple models of infection and sepsis. Mice lacking Gpr37 exhibited increased death and/or hypothermia following challenge by lipopolysaccharide (LPS), Listeria bacteria, and the mouse malaria parasite Plasmodium berghei. Sepsis induced by LPS and Listeria in wild-type mice is protected by artesunate (ARU) and neuroprotectin D1 (NPD1), but the protective actions of these agents are lost in Gpr37 -/- mice. Notably, we found that ARU binds to GPR37 in macrophages and promotes phagocytosis and clearance of pathogens. Moreover, ablation of macrophages potentiated infection, sepsis, and their sequelae, whereas adoptive transfer of NPD1- or ARU-primed macrophages reduced infection, sepsis, and pain-like behaviors. Our findings reveal physiological actions of ARU in host cells by activating macrophages and suggest that GPR37 agonists may help to treat sepsis, bacterial infections, and malaria. |
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