The COX-2-derived PGE2 autocrine contributes to bradykinin-induced matrix metalloproteinase-9 expression and astrocytic migration via STAT3 signaling

Tsong Hai Lee, Pei Shan Liu, Ming Ming Tsai, Jiun Liang Chen, Su Jane Wang, Hsi Lung Hsieh*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

13 Scopus citations

Abstract

Background: The matrix metalloproteinase-9 (MMP-9) is up-regulated by several proinflammatory mediators in the central nervous system (CNS) diseases. Increasing reports show that MMP-9 expression is an inflammatory biomarker of several CNS disorders, including the CNS inflammation and neurodegeneration. Bradykinin (BK) is a common proinflammatory mediator and elevated in several brain injury and inflammatory disorders. The raised BK may be detrimental effects on the CNS that may aggravate brain inflammation through MMP-9 up-regulation or cyclooxygenase-2 (COX-2)-derived prostaglandin E2 (PGE2) production in brain astrocytes. However, the relationship between BK-induced MMP-9 expression and COX-2-derived PGE2 release in brain astrocytes remains unclear. Methods: Herein we used rat brain astrocytes (RBA) to investigate the role of the COX-2/PGE2 system in BK-induced MMP-9 expression. We used zymographic, RT-PCR, EIA, and Western blotting analyses to confirm that BK induces MMP-9 expression via a COX-2/PGE2-dependent pathway. Results: Our results show activation of native COX-2 by BK led to PGE2 production and release. Subsequently, PGE2 induced MMP-9 expression via PGE2 receptor (EP)-mediated c-Src, Jak2, ERK1/2, and then activated signal transducer and activator of transcription 3 (STAT3) signaling pathway. Finally, up-regulation of MMP-9 by BK via the pathway may promote astrocytic migration. Conclusion: These results demonstrated that a novel autocrine pathway for BK-induced MMP-9 protein expression is mediated through activation of STAT3 by native COX-2/PGE2-mediated c-Src/Jak2/ERK cascades in brain astrocytes. [MediaObject not available: see fulltext.]

Original languageEnglish
Article number185
JournalCell Communication and Signaling
Volume18
Issue number1
DOIs
StatePublished - 12 2020

Bibliographical note

Publisher Copyright:
© 2020, The Author(s).

Keywords

  • Bradykinin
  • Brain astrocytes
  • COX-2/PGE autocrine
  • Matrix metalloproteinase-9
  • Neuroinflammation
  • STAT3

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