title: Ephedrine hydrochloride inhibits PGN-induced inflammatory responses by promoting IL-10 production and decreasing proinflammatory cytokine secretion via the PI3K/Akt/GSK3β pathway.
abstract: Approaches for controlling inflammatory responses and reducing the mortality rate of septic patients remain clinically ineffective; new drugs need to be identified that can induce anti-inflammatory responses. Ephedrine hydrochloride (EH) is a compound that is widely used in cardiovascular diseases, especially to treat hypotension caused by either anesthesia or overdose of antihypertensive drugs. In this study, we reported that EH also plays an important role in the control of the inflammatory response. EH increased IL-10 and decreased proinflammatory cytokine (IL-6, tumor-necrosis factor (TNF)-α, IL-12 and IL-1β) expression in primary peritoneal macrophages and Raw264.7 cells treated with peptidoglycan (PGN), a Gram-positive cell wall component. The anti-inflammatory role of EH was also demonstrated in an experimental mouse model of peritonitis induced by intraperitoneal PGN injection. The phosphatidylinositol 3-kinase (PI3K)/Akt pathway was found to be responsible for the EH-mediated increase in IL-10 production and decrease in IL-6 expression. Therefore, our results illustrated that EH can help maintain immune equilibrium and diminish host damage by balancing the production of pro- and anti-inflammatory cytokines after PGN challenge. EH may be a new potential anti-inflammatory drug that can be useful for treating severe invasive Gram-positive bacterial infection.
authors.affiliation: Department of Immunology and Microbiology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Yuejuan
authors.initials: Y
authors.lastname: Zheng
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Yuhu
authors.initials: Y
authors.lastname: Li
authors.forename: Limin
authors.initials: L
authors.lastname: Xu
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Ziyi
authors.initials: Z
authors.lastname: Guo
authors.forename: Haiyan
authors.initials: H
authors.lastname: Song
authors.forename: Muyi
authors.initials: M
authors.lastname: Yang
authors.forename: Beier
authors.initials: B
authors.lastname: Luo
authors.forename: Aoxiang
authors.initials: A
authors.lastname: Zheng
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Guang
authors.initials: G
authors.lastname: Ji
authors.forename: Yizhi
authors.initials: Y
authors.lastname: Yu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004809:Ephedrine / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010457:Peptidoglycan / Q000008:administration & dosage / Q000276:immunology; D010538:Peritonitis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D018805:Sepsis / Q000188:drug therapy* / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D018836:Inflammation Mediators; D010457:Peptidoglycan; D016753:Interleukin-10; D019869:Phosphatidylinositol 3-Kinases; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D004809:Ephedrine