Transient early neurotrophin release and delayed inflammatory cytokine release by microglia in response to PAR-2 stimulation

Journal of Neuroinflammation

Hong-bin Yuan¹  Dian-wen Song²  Fang-ting Liu¹  Ji-hu Sun³  Qing Ouyang¹  Qian-bo Chen⁴  Chen-wen Chen¹ 

[1] Department of Anesthesiology, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China;Department of Orthopedics, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China;Department of Physiology, College of Basic Medical Sciences, Second Military Medical University, Shanghai, 200433, China;Department of Anesthesiology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200433, China

关键词: Neuronal cell death;    NO;    BDNF;    Microglia;    PAR-2;   

Others  :  1212493
DOI  :  10.1186/1742-2094-9-142

 received in 2011-12-09, accepted in 2012-05-23,  发布年份 2012

【 摘 要 】

Activated microglia exerts both beneficial and deleterious effects on neurons, but the signaling mechanism controlling these distinct responses remain unclear. We demonstrated that treatment of microglial cultures with the PAR-2 agonist, 2-Furoyl-LIGRLO-NH2, evoked early transient release of BDNF, while sustained PAR-2 stimulation evoked the delayed release of inflammatory cytokines (IL-1β and TNF-α) and nitric oxide. Culture medium harvested during the early phase (at 1 h) of microglial activation induced by 2-Furoyl-LIGRLO-NH2 (microglial conditioned medium, MCM) had no deleterious effects on cultured neurons, while MCM harvested during the late phase (at 72 h) promoted DNA fragmentation and apoptosis as indicated by TUNEL and annexin/PI staining. Blockade of PAR-1 during the early phase of PAR-2 stimulation enhanced BDNF release (by 11%, small but significant) while a PAR-1 agonist added during the late phase (24 h after 2-Furoyl-LIGRLO-NH2 addition) suppressed the release of cytokines and NO. The neuroprotective and neurotoxic effects of activated microglial exhibit distinct temporal profiles that are regulated by PAR-1 and PAR-2 stimulation. It may be possible to facilitate neuronal recovery and repair by appropriately timed stimulation and inhibition of microglial PAR-1 and PAR-2 receptors.

【 授权许可】

   
2012 Chen et al.; licensee BioMed Central Ltd.

【 图 表 】

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