title: Effects of IL-2 on MMP expression in freshly isolated human NK cells and the IL-2-independent NK cell line YT.
abstract: Interleukin-2 is an important activation factor for natural killer (NK) cells but its effect on NK cell matrix metalloproteinases (MMP) production and matrix degradation is less well investigated. We have used freshly isolated human NK cells and the IL-2-independent NK cell line, YT, to investigate the effects of IL-2 stimulation on NK cell invasion of Matrigel and on MMP expression and production. In YT cells, we found opposing early and late effects of IL-2 stimulation with an early (2 h) increase in MMP-9 protein level and enhanced migration in the Matrigel invasion assay and by 30 hours a decreased mRNA expression of MMP-2, MMP-9, MMP-13, MT3-MMP, and MT6-MMP. We also found a preculture period of 48 hours with IL-2 to negatively affect YT cell migration. We furthermore found that freshly isolated human NK cells Matrigel invasion was MMP-dependent and it increased in response to IL-2. Importantly, in freshly isolated human NK cells we did not see a downregulation of MMPs after 24 hours IL-2 stimulation, but instead a significant upregulation of MT6-MMP mRNA. Because of the cellular localisation of MT6-MMP, which ensures a focalized proteolytic activity, and its high expression compared with the other MMPs in freshly isolated human NK cells makes it of interest to study further.
authors.affiliation: Department of Oncology, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Edsparr
authors.forename: Frank M
authors.initials: FM
authors.lastname: Speetjens
authors.forename: Adri
authors.initials: A
authors.lastname: Mulder-Stapel
authors.forename: Ronald H
authors.initials: RH
authors.lastname: Goldfarb
authors.forename: Per H
authors.initials: PH
authors.lastname: Basse
authors.forename: Bo
authors.initials: B
authors.lastname: Lennernäs
authors.forename: Peter J K
authors.initials: PJ
authors.lastname: Kuppen
authors.forename: Per
authors.initials: P
authors.lastname: Albertsson
mesh_terms: D018929:Cell Culture Techniques; D002460:Cell Line; D002465:Cell Movement; D002469:Cell Separation; D003094:Collagen; D004338:Drug Combinations; D006801:Humans; D007114:Immunization; D007376:Interleukin-2 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D007797:Laminin; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D011509:Proteoglycans
chemical_list: D004338:Drug Combinations; D007376:Interleukin-2; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen; D020782:Matrix Metalloproteinases
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