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 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.
Edsparr
Karin
K
Department of Oncology, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.
Speetjens
Frank M
FM
Mulder-Stapel
Adri
A
Goldfarb
Ronald H
RH
Basse
Per H
PH
Lennernäs
Bo
B
Kuppen
Peter J K
PJ
Albertsson
Per
P
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
D004338:Drug Combinations; D007376:Interleukin-2; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen; D020782:Matrix Metalloproteinases
In Vivo. 2000 Jan-Feb;14(1):269-76
10757086
Clin Exp Metastasis. 2000;18(2):189-96
11235995
Histochem Cell Biol. 2001 Jan;115(1):67-72
11219610
J Immunol. 2000 Jun 1;164(11):5883-9
10820269
Am J Pathol. 2006 Aug;169(2):445-58
16877347
Scand J Immunol. 2001 Feb;53(2):103-10
11169213
Immunol Cell Biol. 2009 Aug-Sep;87(6):489-95
19434071
Int J Cancer. 2003 Jul 1;105(4):512-9
12712443
Scand J Immunol. 2007 Oct;66(4):402-9
17850584
Trends Immunol. 2003 Nov;24(11):603-9
14596885
In Vivo. 2000 Sep-Oct;14(5):565-70
11125540
Int J Cancer. 1993 Mar 12;53(5):850-5
8449611
Immunology. 2000 Jul;100(3):378-83
10929061
J Immunol. 1997 Mar 1;158(5):2327-33
9036981
In Vivo. 2000 Sep-Oct;14(5):557-64
11125539
J Immunol. 1985 Mar;134(3):1623-30
2578514
Biochemistry. 1996 Jun 4;35(22):7159-64
8679543
J Immunol. 1998 May 1;160(9):4248-53
9574526
Biochem Soc Symp. 2003;(70):277-85
14587300
FEBS Lett. 2004 Jul 2;569(1-3):156-60
15225625