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

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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.

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Acknowledgments

This work is supported in part by grants from the National Science Council (NSC 102-2320-B-039-051-MY3, NSC 102-2320-B-039-026-MY3, NSC 103-2811-B-039-021, and NSC 104-2320-B-468 -002), China Medical University (CMU103-ASIA-02), and Taiwan Ministry of Health and Welfare Clinical Trial and Research Center of Excellence (MOHW104-TDU-B-212-113002). The authors thank Ms Y.-R Chen and Ms S.-H. Ko for the technical support.

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    Authors and Affiliations

    1. Department of General Surgery, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan

      Jia-Hong Chen

    2. School of Medicine, Tzu Chi University, Hualien, Taiwan

      Jia-Hong Chen

    3. Department of Neurology, China Medical University Hospital, Taichung, Taiwan

      Chon-Haw Tsai

    4. Graduate Institute of Neural and Cognitive Sciences, China Medical University, No.91 Hsueh-Shih Road, Taichung, Taiwan

      Chon-Haw Tsai, Hsiao-Yun Lin, Chien-Fang Huang, Yuk-Man Leung & Dah-Yuu Lu

    5. Graduate Institute of Basic Medical Science, College of Medicine, China Medical University, Taichung, Taiwan

      Sheng-Wei Lai

    6. Department of Biotechnology, Asia University, Taichung, Taiwan

      Cheng-Fang Tsai

    7. Department of Bioinformatics, Asia University, Taichung, Taiwan

      Pei-Chun Chang

    8. Department of Photonics and Communication Engineering, Asia University, Taichung, Taiwan

      Dah-Yuu Lu

    9. Department of Physiology, School of Medicine, China Medical University, No.91 Hsueh-Shih Road, Taichung, Taiwan

      Chingju Lin

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    Chen, JH., Tsai, CH., Lin, HY. et al. Interlukin-18 Is a Pivot Regulatory Factor on Matrix Metalloproteinase-13 Expression and Brain Astrocytic Migration. Mol Neurobiol 53, 6218–6227 (2016). https://doi.org/10.1007/s12035-015-9529-z

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