RT Journal Article
SR Electronic
T1 Propofol inhibits endogenous formyl peptide-induced neutrophil activation and alleviates lung injury
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 340711
DO 10.1101/340711
A1 Chun-Yu Chen
A1 Yung-Fong Tsai
A1 Wei-Ju Huang
A1 Shih-Hsin Chang
A1 Tsong-Long Hwang
YR 2018
UL http://biorxiv.org/content/early/2018/06/06/340711.abstract
AB Critically ill patients have a high risk of sepsis. Various studies have demonstrated that propofol has anti-inflammatory effects that may benefit critically ill patients who require anesthesia. However, the mechanism and therapeutic effect remain incompletely understood. Our previous data suggest that propofol can act as a formyl peptide receptor 1 (FPR1) antagonist. Here, we hypothesize that propofol mitigates sepsis-induced acute lung injury (ALI) by inhibiting mitochondria-derived N-formyl peptide-mediated neutrophil activation. In human neutrophils, propofol competitively reduced the release of elastase, superoxide, and reactive oxygen species induced by fMMYALF, a human mitochondria-derived N-formyl peptide. In addition, propofol significantly inhibited fMMYALF-induced chemotaxis, calcium mobilization, and phosphorylation of protein kinase B and mitogen-activated protein kinases. These results indicate that propofol suppresses neutrophil activation by blocking the interaction between endogenous N-formyl peptide and its receptor, FPR1, thus inhibiting downstream signaling. Furthermore, propofol alleviated alveolar wall disruption, edematous changes, and neutrophil infiltration in lipopolysaccharide-induced ALI in mice. Noticeably, propofol improved the survival of sepsis mice. This study indicates that the anti-neutrophil effects of propofol may benefit critically ill septic patients.