title: Mechanisms involved in enhancement of matrix metalloproteinase-9 expression in macrophages by interleukin-33.
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.
authors.affiliation: Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental University, Kitakyushu, Fukuoka, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Ariyoshi
authors.affiliation: Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental University, Kitakyushu, Fukuoka, Japan.
authors.forename: Toshinori
authors.initials: T
authors.lastname: Okinaga
authors.affiliation: Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental University, Kitakyushu, Fukuoka, Japan.|Division of Developmental Stomatognathic Function Science, Kyushu Dental University, Kitakyushu, Fukuoka, Japan.
authors.forename: Wichida
authors.initials: W
authors.lastname: Chaweewannakorn
authors.affiliation: Units of Education on Healthcare Team, School of Oral Health Science, Kyushu Dental University, Kitakyushu, Fukuoka, Japan.
authors.forename: Sumio
authors.initials: S
authors.lastname: Akifusa
authors.affiliation: Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental University, Kitakyushu, Fukuoka, Japan.
authors.forename: Tatsuji
authors.initials: T
authors.lastname: Nisihara
mesh_terms: D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D000067596:Interleukin-33 / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D000067996:RAW 264.7 Cells; D034622:RNA Interference; D017472:Receptors, Interleukin-1 / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D057705:Transendothelial and Transepithelial Migration / Q000187:drug effects; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; C506536:IL33 protein, human; D000067596:Interleukin-33; D016328:NF-kappa B; D017472:Receptors, Interleukin-1; C530318:ST2L protein, mouse; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D048049:Extracellular Signal-Regulated MAP Kinases; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse
keywords: activator protein 1 (AP-1); interleukin-33 (IL-33); macrophage; matrix metalloproteinase-9 (MMP-9); nuclear factor-kappa B (NF-κB)