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

Joint Authors

He, Shaoheng
Zeng, Xiaoning
Yang, Haiwei
Zhang, Shu
Xu, Luwei

Source

Mediators of Inflammation

Issue

Vol. 2013, Issue 2013 (31 Dec. 2013), pp.1-10, 10 p.

Publisher

Hindawi Publishing Corporation

Publication Date

2013-06-02

Country of Publication

Egypt

No. of Pages

10

Main Subjects

Diseases

Abstract EN

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.

American Psychological Association (APA)

Zeng, Xiaoning& Zhang, Shu& Xu, Luwei& Yang, Haiwei& He, Shaoheng. 2013. Activation of Protease-Activated Receptor 2-Mediated Signaling by Mast Cell Tryptase Modulates Cytokine Production in Primary Cultured Astrocytes. Mediators of Inflammation،Vol. 2013, no. 2013, pp.1-10.
https://search.emarefa.net/detail/BIM-448980

Modern Language Association (MLA)

Xu, Luwei…[et al.]. Activation of Protease-Activated Receptor 2-Mediated Signaling by Mast Cell Tryptase Modulates Cytokine Production in Primary Cultured Astrocytes. Mediators of Inflammation No. 2013 (2013), pp.1-10.
https://search.emarefa.net/detail/BIM-448980

American Medical Association (AMA)

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. Mediators of Inflammation. 2013. Vol. 2013, no. 2013, pp.1-10.
https://search.emarefa.net/detail/BIM-448980

Data Type

Journal Articles

Language

English

Notes

Includes bibliographical references

Record ID

BIM-448980