Deficiency of Growth Hormone Secretagogue Receptor in Myeloid Cells Attenuate the Neuroinflammation of CLP-Induced Sepsis

Abstract

Sepsis is a threat to human healthy and caused by infection with a systemic inflammatory response. Sepsis ranges from endotoxemia to more severe and long-term effects. Moreover, the low blood pressure and inflammation patients experience during sepsis may lead to brain damage and cause cognitive problem. Growth hormone secretagogue receptor (GHS-R) is recognized as ghrelin receptor which is a G-protein coupled receptor. We previously reported that mice with global GHS-R ablation plays important roles in macrophage polarization during aging and diet induced inflammation. Thus, we created LysM-Cre;Ghsrflox/flox mice to determine the role of GHS-R in myeloid cells. Remarkably, we detected that deletion of GHS-R in myeloid cells ameliorates neuroinflammation and protects brain from septic shock-induced behavioral impairments. Obviously, we found that significantly decreasing of M1-like macrophages and increasing of M2-like macrophages in the brain of these septic mice, consistently found reduced expression of pro-inflammation cytokines. In conclusion, our data indicated that GHS-R ablation in myeloid cells protects against sepsis, improve survival ratio, and mitigating the brain inflammation. In this project, I aim to reveal the pathobiology of sepsis and whether GHS-R can be a treatment strategy for sepsis-induced neuroinflammation.