title: Programmed death (PD)-1 attenuates macrophage activation and brain inflammation via regulation of fibrinogen-like protein 2 (Fgl-2) after intracerebral hemorrhage in mice.
abstract: Neuroinflammation plays an important role in the recovery of brain injury in ICH. Macrophage is the major executor in the neuroinflammation and initiates neurological defects. Programmed death 1 (PD-1) delivers inhibitory signals that regulate the balance between T cell activation, tolerance, and immunopathology. PD-1 expression by macrophages plays a pathologic role in the innate inflammatory response. However, the exact role of PD-1 on inflammatory responses following ICH has not been well identified. In this experiment, PD-1 KO (PD-1 -/-) ICH mice and Wild-type (WT) ICH mice were caused by intracranial injection of type IV collagenase. The level of macrophage activation, inflammatory cytokines and fibrinogen-like protein 2 (Fgl-2) were detected using immunofluorescence staining and ELISA assays. In addition, brain edema and neurological scores of ICH mice were also measured. Our data demonstrated that ICH promoted PD-1 expression of macrophage and enhanced inflammatory cytokines and Fgl-2 concentrations. PD-1 -/- mice exhibited significantly higher expression of the inflammatory cytokines which initiate Fgl-2, than did their wild-type (WT) littermates. As a result, macrophage activation, cerebral edema and neurological deficit scores of PD-1 -/- mice were higher. In conclusion, our data demonstrate that PD-1 plays a vital role in brain inflammation via regulation of Fgl-2 after ICH, and that manipulation of PD-1 might be a promising therapeutical target in ICH.
authors.affiliation: Department of Neurosurgery, The 476th Hospital of PLA, Fuzhou, Fujian, 350025, China.
authors.forename: Bangqing
authors.initials: B
authors.lastname: Yuan
authors.affiliation: Department of Neurosurgery, The 476th Hospital of PLA, Fuzhou, Fujian, 350025, China.
authors.forename: Shaokuan
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Neurosurgery, The 476th Hospital of PLA, Fuzhou, Fujian, 350025, China.
authors.forename: Shuangfeng
authors.initials: S
authors.lastname: Gong
authors.affiliation: Department of Neurosurgery, The 476th Hospital of PLA, Fuzhou, Fujian, 350025, China.
authors.forename: Feihong
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, The 476th Hospital of PLA, Fuzhou, Fujian, 350025, China.
authors.forename: Li
authors.initials: L
authors.lastname: Lin
authors.affiliation: Department of Neurosurgery, The 476th Hospital of PLA, Fuzhou, Fujian, 350025, China.
authors.forename: Tonggang
authors.initials: T
authors.lastname: Su
authors.affiliation: Department of Neurosurgery, The 476th Hospital of PLA, Fuzhou, Fujian, 350025, China.
authors.forename: Hanchao
authors.initials: H
authors.lastname: Sheng
authors.affiliation: Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing, 402160, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing, 402160, China.
authors.forename: Kunlong
authors.initials: K
authors.lastname: Ma
authors.affiliation: Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing, 402160, China. Electronic address: yangzhao5140@sohu.com.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Yang
mesh_terms: D000818:Animals; D002543:Cerebral Hemorrhage / Q000150:complications* / Q000209:etiology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004660:Encephalitis / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D005340:Fibrinogen / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000378:metabolism; D008262:Macrophage Activation / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics / Q000378:metabolism*
chemical_list: D016207:Cytokines; C490637:Fgl2 protein, mouse; D018836:Inflammation Mediators; D061026:Programmed Cell Death 1 Receptor; D005340:Fibrinogen
keywords: Fgl-2; ICH; Inflammation; Macrophage; PD-1