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Interlukin-18 Is a Pivot Regulatory Factor on Matrix Metalloproteinase-13 Expression and Brain Astrocytic Migration
- Source :
- Molecular neurobiology. 53(9)
- Publication Year :
- 2015
-
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.
- Subjects :
- 0301 basic medicine
Neuroscience (miscellaneous)
Matrix metalloproteinase
Rats, Sprague-Dawley
03 medical and health sciences
Cellular and Molecular Neuroscience
Mice
Phosphatidylinositol 3-Kinases
0302 clinical medicine
Cell Movement
Matrix Metalloproteinase 13
medicine
Animals
Protein kinase B
Microglia
business.industry
Kinase
Interleukin-18
JNK Mitogen-Activated Protein Kinases
Interleukin
Brain
Cell migration
Cell biology
Up-Regulation
Transcription Factor AP-1
Protein Kinase C-delta
030104 developmental biology
medicine.anatomical_structure
Neurology
Astrocytes
Immunology
Phosphorylation
Signal transduction
business
Proto-Oncogene Proteins c-akt
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 15591182
- Volume :
- 53
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- Molecular neurobiology
- Accession number :
- edsair.doi.dedup.....f05d8ae89ab8e5ebaead36ddfcf1b330