title: Interlukin-18 Is a Pivot Regulatory Factor on Matrix Metalloproteinase-13 Expression and Brain Astrocytic Migration.
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.
authors.affiliation: Department of General Surgery, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan.|School of Medicine, Tzu Chi University, Hualien, Taiwan.
authors.forename: Jia-Hong
authors.initials: JH
authors.lastname: Chen
authors.affiliation: Department of Neurology, China Medical University Hospital, Taichung, Taiwan.|Graduate Institute of Neural and Cognitive Sciences, China Medical University, No.91 Hsueh-Shih Road, Taichung, Taiwan.
authors.forename: Chon-Haw
authors.initials: CH
authors.lastname: Tsai
authors.affiliation: Graduate Institute of Neural and Cognitive Sciences, China Medical University, No.91 Hsueh-Shih Road, Taichung, Taiwan.
authors.forename: Hsiao-Yun
authors.initials: HY
authors.lastname: Lin
authors.affiliation: Graduate Institute of Neural and Cognitive Sciences, China Medical University, No.91 Hsueh-Shih Road, Taichung, Taiwan.
authors.forename: Chien-Fang
authors.initials: CF
authors.lastname: Huang
authors.affiliation: Graduate Institute of Neural and Cognitive Sciences, China Medical University, No.91 Hsueh-Shih Road, Taichung, Taiwan.
authors.forename: Yuk-Man
authors.initials: YM
authors.lastname: Leung
authors.affiliation: Graduate Institute of Basic Medical Science, College of Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Sheng-Wei
authors.initials: SW
authors.lastname: Lai
authors.affiliation: Department of Biotechnology, Asia University, Taichung, Taiwan.
authors.forename: Cheng-Fang
authors.initials: CF
authors.lastname: Tsai
authors.affiliation: Department of Bioinformatics, Asia University, Taichung, Taiwan.
authors.forename: Pei-Chun
authors.initials: PC
authors.lastname: Chang
authors.affiliation: Graduate Institute of Neural and Cognitive Sciences, China Medical University, No.91 Hsueh-Shih Road, Taichung, Taiwan. dahyuu@mail.cmu.edu.tw.|Department of Photonics and Communication Engineering, Asia University, Taichung, Taiwan. dahyuu@mail.cmu.edu.tw.
authors.forename: Dah-Yuu
authors.initials: DY
authors.lastname: Lu
authors.affiliation: Department of Physiology, School of Medicine, China Medical University, No.91 Hsueh-Shih Road, Taichung, Taiwan. clin33@mail.cmu.edu.tw.
authors.forename: Chingju
authors.initials: C
authors.lastname: Lin
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000378:metabolism*; D001921:Brain / Q000166:cytology*; D002465:Cell Movement; D020382:Interleukin-18 / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism*; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051745:Protein Kinase C-delta / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D018808:Transcription Factor AP-1 / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D020382:Interleukin-18; D018808:Transcription Factor AP-1; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051745:Protein Kinase C-delta; D048031:JNK Mitogen-Activated Protein Kinases; D053509:Matrix Metalloproteinase 13
keywords: Astrocytes; IL-18; MMP-13; Microglia; Migration