RRC ID 52065
Author Ariyoshi W, Okinaga T, Chaweewannakorn W, Akifusa S, Nisihara T.
Title Mechanisms involved in enhancement of matrix metalloproteinase-9 expression in macrophages by interleukin-33.
Journal J Cell Physiol
Abstract Endothelial transmigration of macrophages is accomplished by matrix metalloproteinase (MMP)-induced degradation of the basement membrane and extracellular matrix components. Macrophages upregulate MMP-9 expression and secretion upon immunological challenges and require its activity for migration during inflammatory responses. Interleukin (IL)-33 is a recently discovered pro-inflammatory cytokine that belongs to the IL-1 family. The aim of this study was to elucidate the mechanisms underlying IL-33-induced MMP-9 expression in the mouse monocyte/macrophage line RAW264.7. IL-33 increased MMP-9 mRNA and protein expression in RAW264.7 cells. Blockage of IL-33-IL-33 receptor (ST2L) binding suppressed IL-33-mediated induction of MMP-9. IL-33 induced phosphorylation and nuclear translocation of extracellular signal-regulated kinase 1/2 (ERK1/2) and nuclear factor-kappa B (NF-κB). Chromatin immunoprecipitation indicated that IL-33 increased c-fos recruitment to the MMP-9 promoter. Reporter assay findings also revealed that IL-33 stimulated the transcriptional activity of activator protein 1 (AP-1). Pre-treatment of the cells with a specific inhibitor of ERK1/2 and NF-κB attenuated the IL-33-induced activation of AP-1 subunits, transcriptional activity of AP-1, and expression of MMP-9. We also demonstrated that ERK-dependent activation of cAMP response element binding protein (CREB) is a key step for AP-1 activation by IL-33. These results indicate an essential role of ERK/CREB and NF-κB cascades in the induction of MMP-9 in monocytes/macrophages through AP-1 activation.
Volume 232(12)
Pages 3481-3495
Published 2017-12
DOI 10.1002/jcp.25809
PMID 28105703
MeSH Animals Cyclic AMP Response Element-Binding Protein / genetics Cyclic AMP Response Element-Binding Protein / metabolism Dose-Response Relationship, Drug Extracellular Signal-Regulated MAP Kinases / metabolism Interleukin-33 / pharmacology* Macrophages / drug effects* Macrophages / enzymology Matrix Metalloproteinase 9 / genetics Matrix Metalloproteinase 9 / metabolism* Mice NF-kappa B / metabolism Phosphorylation Promoter Regions, Genetic Protein Binding RAW 264.7 Cells RNA Interference Receptors, Interleukin-1 / agonists Receptors, Interleukin-1 / genetics Receptors, Interleukin-1 / metabolism Signal Transduction / drug effects Time Factors Transcription Factor AP-1 / genetics Transcription Factor AP-1 / metabolism Transcription, Genetic Transcriptional Activation Transendothelial and Transepithelial Migration / drug effects Transfection Tumor Necrosis Factor-alpha / genetics Tumor Necrosis Factor-alpha / metabolism Up-Regulation
IF 4.522
Times Cited 10
Human and Animal Cells RAW 264(RCB0535)