Interlukin-18 Is a Pivot Regulatory Factor on Matrix Metalloproteinase-13 Expression and Brain Astrocytic Migration

Jia Hong Chen, Chon Haw Tsai, Hsiao Yun Lin, Chien Fang Huang, Yuk Man Leung, Sheng Wei Lai, Cheng Fang Tsai, Pei Chun Chang, Dah Yuu Lu, Chingju Lin

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

The expression of matrix metalloproteinase-13 (MMP-13) has been shown to be elevated in some pathophysiological conditions and is involved in the degradation of extracellular matrix in astrocytes. In current study, the function of MMP-13 was further investigated. The conditioned medium (CM) collected from activated microglia increased interleukin (IL)-18 production and enhanced MMP-13 expression in astrocytes. Furthermore, treatment with recombinant IL-18 increased MMP-13 protein and mRNA levels in astrocytes. Recombinant IL-18 stimulation also increased the enzymatic activity of MMP-13 and the migratory activity of astrocytes, while administration of MMP-13 or pan-MMP inhibitors antagonized IL-18-induced migratory activity of astrocytes. In addition, administration of recombinant IL-18 to astrocytes led to the phosphorylation of JNK, Akt, or PKCδ, and treatment of astrocytes with JNK, PI3 kinase/Akt, or PKCδ inhibitors significantly decreased the IL-18-induced migratory activity. Taken together, the results suggest that IL-18-induced MMP-13 expression in astrocytes is regulated by JNK, PI3 kinase/Akt, and PKCδ signaling pathways. These findings also indicate that IL-18 is an important regulator leading to MMP-13 expression and cell migration in astrocytes.

Original languageEnglish
Pages (from-to)6218-6227
Number of pages10
JournalMolecular Neurobiology
Volume53
Issue number9
DOIs
StatePublished - 1 Nov 2016
Externally publishedYes

Keywords

  • Astrocytes
  • IL-18
  • MMP-13
  • Microglia
  • Migration

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