NDLI: Activation of Protease-Activated Receptor 2-Mediated Signaling by Mast Cell Tryptase Modulates Cytokine Production in Primary Cultured Astrocytes

Content Provider	PubMed Central
Author	Zeng, Xiaoning Zhang, Shu Xu, Luwei Yang, Haiwei He, Shaoheng
Copyright Year	2013
Abstract	Protease-activated receptor 2 (PAR-2), which is abundantly expressed in astrocytes, is known to play major roles in brain inflammation. However, the influence of the natural agonist of PAR-2, tryptase, on proinflammatory mediator releasedfrom astrocytes remains uninvestigated. In the present study, we found that tryptase at lower concentrations modestly reduced intracellular ROS production but significantly increased IL-6 and TNF- α secretion at higher concentrations without affecting astrocytic viability and proliferation. The actions of tryptase were alleviated by specific PAR-2 antagonist FSLLRY-NH2 (FS), indicating that the actions of tryptase were via PAR-2. PI3K/AKT inhibitor LY294002 reversed the effect of tryptase on IL-6 production, whereas inhibitors specific for p38, JNK, and ERK1/2 abolished the effect of tryptase on TNF- α production, suggesting that different signaling pathways are involved. Moreover, tryptase-induced activation of MAPKs and AKT was eliminated by FS, implicating that PAR-2 is responsible for transmitting tryptase biosignals to MAPKs and AKT. Tryptase provoked also expression of TGF- β and CNTF in astrocytes. The present findings suggest for the first time that tryptase can regulate the release of cytokines from astrocytes via PAR-2-MAPKs or PAR-2-PI3K/AKT signaling pathways, which reveals PAR-2 as a new target actively participating in the regulation of astrocytic functions.
Related Links	http://dx.doi.org/10.1155/2013/140812
Starting Page	140812
File Format	PDF
ISSN	09629351
e-ISSN	14661861
Journal	Mediators of Inflammation
Volume Number	2013
Language	English
Publisher	Hindawi Publishing Corporation
Publisher Date	2013-01-01
Access Restriction	Open
Rights Holder	Hindawi Publishing Corporation
Subject Keyword	Immunology Cell Biology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Immunology

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Activation of Protease-Activated Receptor 2-Mediated Signaling by Mast Cell Tryptase Modulates Cytokine Production in Primary Cultured Astrocytes

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Activation of Protease-Activated Receptor 2-Mediated Signaling by Mast Cell Tryptase Modulates Cytokine Production in Primary Cultured Astrocytes