Effects of IL-2 on MMP Expression in Freshly Isolated Human NK Cells and the IL-2-independent NK Cell Line YT

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...

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Published in:	Journal of immunotherapy (1997) Vol. 33; no. 5; pp. 475 - 481
Main Authors:	EDSPARR, Karin, SPEETJENS, Frank M, MULDER-STAPEL, Adri, GOLDFARB, Ronald H, BASSE, Per H, LENNERNDS, Bo, KUPPEN, Peter J. K, ALBERTSSON, Per
Format:	Journal Article
Language:	English
Published:	Hagerstown, MD Lippincott Williams & Wilkins 01-06-2010
Subjects:	Antineoplastic agents Biological and medical sciences Cancer and Oncology Cancer och onkologi Cell Culture Techniques Cell Line Cell Movement Cell Separation Collagen Drug Combinations drug effects genetics Humans Immunization immunology Immunotherapy Interleukin-2 Interleukin-2 - metabolism Killer Cells Killer Cells, Natural - drug effects Killer Cells, Natural - immunology Killer Cells, Natural - metabolism Killer Cells, Natural - pathology Laminin Male Matrix Metalloproteinases Matrix Metalloproteinases - genetics Matrix Metalloproteinases - metabolism Medical sciences metabolism Natural pathology Pharmacology. Drug treatments Protein Transport Proteoglycans Human Enzyme Cytokine Metalloendopeptidases In vitro Gelatinase A Natural killer cell Peptidases MMP Treatment Interleukin 2 Immunotherapy Established cell line NK cell Isolated cell migration Hydrolases Cell migration
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1
ISSN:	1524-9557 1537-4513 1537-4513
DOI:	10.1097/CJI.0b013e3181d372a0