HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lash, G. E. Articles by Bulmer, J. N. Search for Related Content PubMed PubMed Citation Articles by Lash, G. E. Articles by Bulmer, J. N.

Interferon- inhibits extravillous trophoblast cell invasion by a mechanism that involves both changes in apoptosis and protease levels

Gendie E. Lash^*,1, Harry A. Otun^*, Barbara A. Innes^*, Maureen Kirkley^*, Leandro De Oliveira^*, Roger F. Searle, Stephen C. Robson^* and Judith N. Bulmer

Schools of
^* Surgical and Reproductive Sciences,

Clinical and Laboratory Sciences and

Medical Education Development, University of Newcastle upon Tyne, Newcastle upon Tyne, UK

¹Correspondence: School of Surgical and Reproductive Sciences, 3rd Floor, William Leech Bldg., University of Newcastle upon Tyne, Newcastle upon Tyne NE2 4HH, UK. E-mail: g.e.lash{at}ncl.ac.uk

Background: Extravillous trophoblast cell (EVT) invasion of decidua and inner third of the myometrium is critical for a successful pregnancy. Many decidual factors are likely to play a role in regulating this process, including uterine natural killer (uNK) cell-derived cytokines. Hypotheses: 1) uNK cells are a major source of IFN gamma (IFN-) and 2) IFN- inhibits EVT invasion via an increase in EVT apoptosis and/or a decrease in active protease levels. Methods: Total decidual and uNK cells from 8–10 wk and 12–14 wk gestational age were cultured. IFN- mRNA (real-time RT-polymerase chain reaction) and protein levels (FastQuant multicytokine analysis) were determined. EVT invasion in the presence of IFN- or anti-IFN--neutralizing antibodies was assessed. Trophoblast apoptosis and proliferation was assessed in explants by immunohistochemistry for M30 and Ki67. Substrate zymography was performed to determine levels of secreted MMP2, MMP9, and uPA. Results: mRNA and protein for IFN- was detected in both total decidual and uNK cell fractions. Trophoblast invasion was inhibited by IFN-. The level of M30-positive EVT was increased in the presence of IFN- whereas levels of secreted MMP2 were decreased. Conclusions: uNK cells are a source of IFN- within early human pregnancy decidua. Mechanisms of IFN- inhibition of EVT invasion include both increased EVT apoptosis and reduced levels of active proteases.—Lash, G. E., Otun, H. A., Innes, B. A., Kirkley, M., De Oliveira, L., Searle, R. F., Robson, S. C., Bulmer, J. N. Interferon- inhibits extravillous trophoblast cell invasion by a mechanism that involves both changes in apoptosis and protease levels.

Key Words: IFN- • uNK cells

This article has been cited by other articles:

				A. M. Sharkey, L. Gardner, S. Hiby, L. Farrell, R. Apps, L. Masters, J. Goodridge, L. Lathbury, C. A. Stewart, S. Verma, et al. Killer Ig-Like Receptor Expression in Uterine NK Cells Is Biased toward Recognition of HLA-C and Alters with Gestational Age J. Immunol., July 1, 2008; 181(1): 39 - 46. [Abstract] [Full Text] [PDF]

				Y. Hu, R. Tan, C. D. MacCalman, G. Eastabrook, S.-H. Park, J. P. Dutz, and P. von Dadelszen IFN-{gamma}-mediated extravillous trophoblast outgrowth inhibition in first trimester explant culture: a role for insulin-like growth factors Mol. Hum. Reprod., May 1, 2008; 14(5): 281 - 289. [Abstract] [Full Text] [PDF]

				L. K. Harris and J. D. Aplin Vascular Remodeling and Extracellular Matrix Breakdown in the Uterine Spiral Arteries During Pregnancy Reproductive Sciences, December 1, 2007; 14(8_suppl): 28 - 34. [Abstract] [PDF]