RRC ID 51625
Author Sakurai T, Yoshiga D, Ariyoshi W, Okinaga T, Kiyomiya H, Furuta J, Yoshioka I, Tominaga K, Nishihara T.
Title Essential role of mitogen-activated protein kinases in IL-17A-induced MMP-3 expression in human synovial sarcoma cells.
Journal BMC Res Notes
Abstract BACKGROUND:The tumor cells were needed to rearrange the extracellular matrix (ECM) and reorganize their cytoskeleton to facilitate the cell motility during the tumor invasion. The proinflammatory cytokine interleukin-17A (IL-17A) is reported to up-regulate tumor invasiveness via ECM degradation by matrix metalloproteinases (MMPs). However the precise effects of IL-17A-dependent invasion remain to be characterized. The aim of this study was to elucidate the mechanisms underlying IL-17A-induced MMP-3 expression in the human synovial sarcoma cells HS-SY-II.
METHODS:HS-SY-II cells were incubated with IL-17A. In some experiments, the cells were pre-incubated with an anti-IL-17 receptor polyclonal antibody (IL-17R Ab) or inhibitors for signaling cascade prior to addition of IL-17A. The expression of MMP-3 was determined by real-time reverse-transcription polymerase chain reaction (RT-PCR) and western blotting. IL-17R expression in HS-SY-II cells was assessed by immunofluorescence microscopy, while the phosphorylation of signaling molecules was measured by western blotting.
RESULTS:IL-17A increased MMP-3 mRNA and protein expression. HS-SY-II cells express the IL-17R on their surface and blockage of IL-17A-IL-17R binding by IL-17R Ab suppressed IL-17A-mediated induction of MMP-3. IL-17A induced the phosphorylation of three components of the mitogen-activated protein kinase (MAPK) pathway including extracellular signal-regulated kinase 1/2 (ERK1/2), p38 MAPK, and c-Jun NH2-terminal kinase (JNK). Pre-treatment of the cells with inhibitors of ERK1/2, p38 MAPK, and JNK attenuated the IL-17A-induced phosphorylation of activator protein-1 (AP-1) subunits and the expression of MMP-3 mRNA.
CONCLUSION:Our results indicate an essential role for MAPKs in the induction of MMP-3 in synovial sarcoma cells, through AP-1 activation.
Volume 9
Pages 68
Published 2016-2-5
DOI 10.1186/s13104-016-1892-y
PII 10.1186/s13104-016-1892-y
PMID 26850593
PMC PMC4743089
MeSH Cell Line, Tumor Humans Interleukin-17 / metabolism* Matrix Metalloproteinase 3 / metabolism* Mitogen-Activated Protein Kinases / metabolism* Protein Kinase Inhibitors / pharmacology Receptors, Interleukin-17 / metabolism Sarcoma, Synovial / enzymology* Sarcoma, Synovial / pathology Transcription Factor AP-1 / metabolism
Human and Animal Cells HS-SY-II(RCB2231)