Localization of matrix metalloproteinase (MMP)-2, MMP-9 and tissue inhibitors for MMPs (TIMPs) in uterine natural killer cells in early human pregnancy

Invasion by extravillous trophoblast into uterine decidua and myometrium with remodeling of spiral arteries is essential for normal human pregnancy and is tightly regulated. Uterine natural killer (uNK) cells appear to be a major maternal regulator of placentation through the secretion of growth fac...

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Veröffentlicht in:	Human reproduction (Oxford) Jg. 24; H. 3; S. 553
Hauptverfasser:	Naruse, Katsuhiko, Lash, Gendie E, Innes, Barbara A, Otun, Harry A, Searle, Roger F, Robson, Stephen C, Bulmer, Judith N
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	England 01.03.2009
Schlagworte:	Biopsy CD56 Antigen - biosynthesis Female Gelatinases - metabolism Gene Expression Regulation, Enzymologic Humans Immunohistochemistry - methods Killer Cells, Natural - metabolism Matrix Metalloproteinase 2 - biosynthesis Matrix Metalloproteinase 9 - biosynthesis Myometrium - metabolism Pregnancy Tissue Inhibitor of Metalloproteinases - metabolism Trophoblasts - metabolism Uterus - metabolism
ISSN:	1460-2350, 1460-2350
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Abstract	Invasion by extravillous trophoblast into uterine decidua and myometrium with remodeling of spiral arteries is essential for normal human pregnancy and is tightly regulated. Uterine natural killer (uNK) cells appear to be a major maternal regulator of placentation through the secretion of growth factors, cytokines and proteinases. Matrix metalloproteinase (MMP)-2 and MMP-9 activity in placental bed biopsies was studied using in situ gelatin zymography. Expression by uNK cells of MMP-2, MMP-9 and their tissue inhibitors, TIMP-1, TIMP-2 and TIMP-3, was localized in the placental bed by immunohistochemistry. Levels of MMP-2, MMP-9, TIMP-1, TIMP-2 and TIMP-3 secreted into 24 h cell culture supernatants of isolated uNK and unseparated (total) decidual cells (8-10 and 12-14 weeks gestation, n = 10 each group) were determined by gelatin gel zymography or western blot as appropriate. Gelatinase activity in situ appeared greater in decidua than myometrium. uNK cells showed strong immunostaining for MMP-2 and TIMP-2. MMP-9 activity was lower in uNK cells than total decidual supernatants (8-10 weeks: P = 0.0003; 12-14 weeks: P = 0.0012). In contrast, there was no difference in MMP-2 secreted by either uNK cell or total decidual cultures. uNK cells from early human pregnancy decidua possess innate protease activity, especially MMP-2, providing further evidence for a role for these cells in regulation of trophoblast invasion and spiral artery remodeling in early placentation.
AbstractList	Invasion by extravillous trophoblast into uterine decidua and myometrium with remodeling of spiral arteries is essential for normal human pregnancy and is tightly regulated. Uterine natural killer (uNK) cells appear to be a major maternal regulator of placentation through the secretion of growth factors, cytokines and proteinases.BACKGROUNDInvasion by extravillous trophoblast into uterine decidua and myometrium with remodeling of spiral arteries is essential for normal human pregnancy and is tightly regulated. Uterine natural killer (uNK) cells appear to be a major maternal regulator of placentation through the secretion of growth factors, cytokines and proteinases.Matrix metalloproteinase (MMP)-2 and MMP-9 activity in placental bed biopsies was studied using in situ gelatin zymography. Expression by uNK cells of MMP-2, MMP-9 and their tissue inhibitors, TIMP-1, TIMP-2 and TIMP-3, was localized in the placental bed by immunohistochemistry. Levels of MMP-2, MMP-9, TIMP-1, TIMP-2 and TIMP-3 secreted into 24 h cell culture supernatants of isolated uNK and unseparated (total) decidual cells (8-10 and 12-14 weeks gestation, n = 10 each group) were determined by gelatin gel zymography or western blot as appropriate.METHODMatrix metalloproteinase (MMP)-2 and MMP-9 activity in placental bed biopsies was studied using in situ gelatin zymography. Expression by uNK cells of MMP-2, MMP-9 and their tissue inhibitors, TIMP-1, TIMP-2 and TIMP-3, was localized in the placental bed by immunohistochemistry. Levels of MMP-2, MMP-9, TIMP-1, TIMP-2 and TIMP-3 secreted into 24 h cell culture supernatants of isolated uNK and unseparated (total) decidual cells (8-10 and 12-14 weeks gestation, n = 10 each group) were determined by gelatin gel zymography or western blot as appropriate.Gelatinase activity in situ appeared greater in decidua than myometrium. uNK cells showed strong immunostaining for MMP-2 and TIMP-2. MMP-9 activity was lower in uNK cells than total decidual supernatants (8-10 weeks: P = 0.0003; 12-14 weeks: P = 0.0012). In contrast, there was no difference in MMP-2 secreted by either uNK cell or total decidual cultures.RESULTSGelatinase activity in situ appeared greater in decidua than myometrium. uNK cells showed strong immunostaining for MMP-2 and TIMP-2. MMP-9 activity was lower in uNK cells than total decidual supernatants (8-10 weeks: P = 0.0003; 12-14 weeks: P = 0.0012). In contrast, there was no difference in MMP-2 secreted by either uNK cell or total decidual cultures.uNK cells from early human pregnancy decidua possess innate protease activity, especially MMP-2, providing further evidence for a role for these cells in regulation of trophoblast invasion and spiral artery remodeling in early placentation.CONCLUSIONSuNK cells from early human pregnancy decidua possess innate protease activity, especially MMP-2, providing further evidence for a role for these cells in regulation of trophoblast invasion and spiral artery remodeling in early placentation. Invasion by extravillous trophoblast into uterine decidua and myometrium with remodeling of spiral arteries is essential for normal human pregnancy and is tightly regulated. Uterine natural killer (uNK) cells appear to be a major maternal regulator of placentation through the secretion of growth factors, cytokines and proteinases. Matrix metalloproteinase (MMP)-2 and MMP-9 activity in placental bed biopsies was studied using in situ gelatin zymography. Expression by uNK cells of MMP-2, MMP-9 and their tissue inhibitors, TIMP-1, TIMP-2 and TIMP-3, was localized in the placental bed by immunohistochemistry. Levels of MMP-2, MMP-9, TIMP-1, TIMP-2 and TIMP-3 secreted into 24 h cell culture supernatants of isolated uNK and unseparated (total) decidual cells (8-10 and 12-14 weeks gestation, n = 10 each group) were determined by gelatin gel zymography or western blot as appropriate. Gelatinase activity in situ appeared greater in decidua than myometrium. uNK cells showed strong immunostaining for MMP-2 and TIMP-2. MMP-9 activity was lower in uNK cells than total decidual supernatants (8-10 weeks: P = 0.0003; 12-14 weeks: P = 0.0012). In contrast, there was no difference in MMP-2 secreted by either uNK cell or total decidual cultures. uNK cells from early human pregnancy decidua possess innate protease activity, especially MMP-2, providing further evidence for a role for these cells in regulation of trophoblast invasion and spiral artery remodeling in early placentation.
Author	Naruse, Katsuhiko Otun, Harry A Lash, Gendie E Robson, Stephen C Innes, Barbara A Searle, Roger F Bulmer, Judith N
Author_xml	– sequence: 1 givenname: Katsuhiko surname: Naruse fullname: Naruse, Katsuhiko organization: Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK – sequence: 2 givenname: Gendie E surname: Lash fullname: Lash, Gendie E – sequence: 3 givenname: Barbara A surname: Innes fullname: Innes, Barbara A – sequence: 4 givenname: Harry A surname: Otun fullname: Otun, Harry A – sequence: 5 givenname: Roger F surname: Searle fullname: Searle, Roger F – sequence: 6 givenname: Stephen C surname: Robson fullname: Robson, Stephen C – sequence: 7 givenname: Judith N surname: Bulmer fullname: Bulmer, Judith N
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/19088110$$D View this record in MEDLINE/PubMed
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SubjectTerms	Biopsy CD56 Antigen - biosynthesis Female Gelatinases - metabolism Gene Expression Regulation, Enzymologic Humans Immunohistochemistry - methods Killer Cells, Natural - metabolism Matrix Metalloproteinase 2 - biosynthesis Matrix Metalloproteinase 9 - biosynthesis Myometrium - metabolism Pregnancy Tissue Inhibitor of Metalloproteinases - metabolism Trophoblasts - metabolism Uterus - metabolism
Title	Localization of matrix metalloproteinase (MMP)-2, MMP-9 and tissue inhibitors for MMPs (TIMPs) in uterine natural killer cells in early human pregnancy
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