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Open Access 01-12-2012 | Research

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

Authors: Chen-wen Chen, Qian-bo Chen, Qing Ouyang, Ji-hu Sun, Fang-ting Liu, Dian-wen Song, Hong-bin Yuan

Published in: Journal of Neuroinflammation | Issue 1/2012

Abstract

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.

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Title: Transient early neurotrophin release and delayed inflammatory cytokine release by microglia in response to PAR-2 stimulation
Authors: Chen-wen Chen
Qian-bo Chen
Qing Ouyang
Ji-hu Sun
Fang-ting Liu
Dian-wen Song
Hong-bin Yuan
Publication date: 01-12-2012
Publisher: BioMed Central
Published in: Journal of Neuroinflammation / Issue 1/2012
Electronic ISSN: 1742-2094
DOI: https://doi.org/10.1186/1742-2094-9-142

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

Abstract

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Abstract

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