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Activation of Protease-Activated Receptor 2-Mediated Signaling by Mast Cell Tryptase Modulates Cytokine Production in Primary Cultured Astrocytes
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,...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3684029/ https://www.ncbi.nlm.nih.gov/pubmed/23818741 http://dx.doi.org/10.1155/2013/140812 |
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author | Zeng, Xiaoning Zhang, Shu Xu, Luwei Yang, Haiwei He, Shaoheng |
author_facet | Zeng, Xiaoning Zhang, Shu Xu, Luwei Yang, Haiwei He, Shaoheng |
author_sort | Zeng, Xiaoning |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3684029 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-36840292013-07-01 Activation of Protease-Activated Receptor 2-Mediated Signaling by Mast Cell Tryptase Modulates Cytokine Production in Primary Cultured Astrocytes Zeng, Xiaoning Zhang, Shu Xu, Luwei Yang, Haiwei He, Shaoheng Mediators Inflamm Research Article 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. Hindawi Publishing Corporation 2013 2013-06-02 /pmc/articles/PMC3684029/ /pubmed/23818741 http://dx.doi.org/10.1155/2013/140812 Text en Copyright © 2013 Xiaoning Zeng et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Zeng, Xiaoning Zhang, Shu Xu, Luwei Yang, Haiwei He, Shaoheng Activation of Protease-Activated Receptor 2-Mediated Signaling by Mast Cell Tryptase Modulates Cytokine Production in Primary Cultured Astrocytes |
title | Activation of Protease-Activated Receptor 2-Mediated Signaling by Mast Cell Tryptase Modulates Cytokine Production in Primary Cultured Astrocytes |
title_full | Activation of Protease-Activated Receptor 2-Mediated Signaling by Mast Cell Tryptase Modulates Cytokine Production in Primary Cultured Astrocytes |
title_fullStr | Activation of Protease-Activated Receptor 2-Mediated Signaling by Mast Cell Tryptase Modulates Cytokine Production in Primary Cultured Astrocytes |
title_full_unstemmed | Activation of Protease-Activated Receptor 2-Mediated Signaling by Mast Cell Tryptase Modulates Cytokine Production in Primary Cultured Astrocytes |
title_short | Activation of Protease-Activated Receptor 2-Mediated Signaling by Mast Cell Tryptase Modulates Cytokine Production in Primary Cultured Astrocytes |
title_sort | activation of protease-activated receptor 2-mediated signaling by mast cell tryptase modulates cytokine production in primary cultured astrocytes |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3684029/ https://www.ncbi.nlm.nih.gov/pubmed/23818741 http://dx.doi.org/10.1155/2013/140812 |
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