title: Triggering Receptor Expressed on Myeloid Cells 2, a Novel Regulator of Immunocyte Phenotypes, Confers Neuroprotection by Relieving Neuroinflammation.
abstract: Microglia can not only detrimentally augment secondary injury but also potentially promote recovery. However, the mechanism underlying the regulation of microglial phenotypes after stroke remains unclear.
  
  
  
  Mice were subjected to middle cerebral artery occlusion for 60 min. At 3 days after reperfusion, the effects of activation and suppression of triggering receptor expressed on myeloid cells 2 on immunocyte phenotypes (n = 5), neurobehavioral scores (n = 7), infarct volumes (n = 8), and neuronal apoptosis (n = 7) were analyzed. In vitro, cultured microglia were exposed to oxygen-glucose deprivation for 4 h. Inflammatory cytokines, cellular viability (n = 8), neuronal apoptosis (n = 7), and triggering receptor expressed on myeloid cells 2 expression (n = 5) were evaluated in the presence or absence of triggering receptor expressed on myeloid cell-specific small interfering RNA or triggering receptor expressed on myeloid cells 2 overexpression lentivirus.
  
  
  
  Triggering receptor expressed on myeloid cells 2 expression in the ischemic penumbra peaked at 3 days after ischemia-reperfusion injury (4.4 ± 0.1-fold, P = 0.0004) and was enhanced in interleukin-4/interleukin-13-treated microglia in vitro (1.7 ± 0.2-fold, P = 0.0119). After oxygen-glucose deprivation, triggering receptor expressed on myeloid cells 2 conferred neuroprotection by regulating the phenotypic conversion of microglia and inflammatory cytokine release. Intraperitoneal administration of triggering receptor expressed on myeloid cells 2 agonist heat shock protein 60 or unilateral delivery of a recombinant triggering receptor expressed on myeloid cells 2 lentivirus into the cerebral ventricle induced a significant neuroprotective effect in mice (apoptotic neurons decreased to 31.3 ± 7.6%; infarct volume decreased to 44.9 ± 5.3%). All values are presented as the mean ± SD.
  
  
  
  Activation or up-regulation of triggering receptor expressed on myeloid cells 2 promoted the phenotypic conversion of microglia and decreased the number of apoptotic neurons. Our study suggests that triggering receptor expressed on myeloid cells 2 is a novel regulator of microglial phenotypes and may be a potential therapeutic target for stroke.
authors.affiliation: From the Departments of Anesthesiology (Q.Z., J.J., S.S., D.Z., L.M., T.J., F.B., L.X.), Orthopedic Surgery (F.L.), and Geriatrics (X.C.), Xijing Hospital, Fourth Military Medical University, Xi'an, China and Department of Anesthesiology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China (Q.Z., Q.W.).
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhai
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.forename: Xiyao
authors.initials: X
authors.lastname: Chen
authors.forename: Ji
authors.initials: J
authors.lastname: Jia
authors.forename: Sisi
authors.initials: S
authors.lastname: Sun
authors.forename: Dandan
authors.initials: D
authors.lastname: Zhou
authors.forename: Lei
authors.initials: L
authors.lastname: Ma
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.forename: Fuhai
authors.initials: F
authors.lastname: Bai
authors.forename: Lize
authors.initials: L
authors.lastname: Xiong
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D018929:Cell Culture Techniques; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D020244:Infarction, Middle Cerebral Artery / Q000503:physiopathology*; D007249:Inflammation / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000378:metabolism; D000066829:Neuroprotection / Q000502:physiology*; D011971:Receptors, Immunologic / Q000378:metabolism*; D015427:Reperfusion Injury / Q000503:physiopathology; D015854:Up-Regulation / Q000502:physiology
chemical_list: D016207:Cytokines; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; C498716:Trem2 protein, mouse