title: TREM-1 expression is increased in human placentas from severe early-onset preeclamptic pregnancies where it may be involved in syncytialization.
abstract: Preeclampsia, a major cause of maternal and perinatal morbidity and mortality, is thought to be attributable to dysregulation of trophoblast invasion and differentiation. Microarray studies have shown that triggering receptor expressed on myeloid cells (TREM) 1, a cell surface molecule involved in the inflammatory response, is increased in preeclamptic placentas. The aim of this study was to determine the level of TREM-1 expression in severe early-onset preeclamptic placentas and its functional role in trophoblast differentiation. Placenta was obtained from women with severe early-onset preeclampsia (n = 19) and gestationally matched preterm controls placentas (n = 8). The TREM-1 expression was determined by quantitative reverse transcriptase polymerase chain reaction and Western blotting. The effect of TREM-1 small interfering RNA on cell fusion and differentiation was assessed in BeWo cells. The effect of oxygen tension on TREM-1 levels, in basal or forskolin-treated BeWo cells, was also assessed. The TREM-1 was localized to the syncytiotrophoblast layer, and TREM-1 messenger RNA and protein expression was significantly increased in preeclamptic placentas. The BeWo cells treated with forskolin were associated with increased TREM-1 expression. The TREM-1 knockdown inhibited forskolin-induced expression of the differentiation marker β-human chorionic gonadotropin but had no effect on the cell-fusion marker E-cadherin. The increase in TREM-1 expression in BeWo cells treated with forskolin during normoxic conditions was reduced in forskolin-treated cells under hypoxic conditions. In conclusion, TREM-1 is increased in preeclamptic placentas and by forskolin treatment. Knockdown of TREM-1 by RNA interference inhibits cell differentiation but has no effect on cell-cell fusion. Finally, we show that TREM-1 upregulation is attenuated under hypoxic conditions in which cell differentiation is impaired.
authors.affiliation: 1Department of Obstetrics and Gynaecology, University of Melbourne, Victoria, Australia.
authors.forename: Ratana
authors.initials: R
authors.lastname: Lim
authors.forename: Gillian
authors.initials: G
authors.lastname: Barker
authors.forename: Martha
authors.initials: M
authors.lastname: Lappas
mesh_terms: D002460:Cell Line; D002470:Cell Survival / Q000502:physiology; D042241:Early Diagnosis; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D010920:Placenta / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000175:diagnosis* / Q000378:metabolism*; D011247:Pregnancy; D011971:Receptors, Immunologic / Q000096:biosynthesis*; D012720:Severity of Illness Index; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D014327:Trophoblasts / Q000378:metabolism*
chemical_list: D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; C408842:TREM1 protein, human; D000073871:Triggering Receptor Expressed on Myeloid Cells-1
keywords: TREM-1; function; placenta; preeclampsia
references.citation: Development. 1991 Nov;113(3):767-77
references.pmid: 1821848
references.citation: Mol Aspects Med. 2007 Apr;28(2):210-9
references.pmid: 17532463
references.citation: J Physiol. 2009 Jul 15;587(Pt 14):3453-8
references.pmid: 19451203
references.citation: Placenta. 2012 Mar;33(3):151-6
references.pmid: 22244735
references.citation: J Cell Sci. 1991 Aug;99 ( Pt 4):681-92
references.pmid: 1769999
references.citation: J Mol Biol. 2004 Sep 24;342(4):1237-48
references.pmid: 15351648
references.citation: J Immunol. 2003 Apr 1;170(7):3812-8
references.pmid: 12646648
references.citation: Placenta. 2011 Feb;32 Suppl:S21-9
references.pmid: 20541258
references.citation: Br J Obstet Gynaecol. 1981 Sep;88(9):876-81
references.pmid: 7272259
references.citation: Taiwan J Obstet Gynecol. 2006 Sep;45(3):189-200
references.pmid: 17175463
references.citation: Rev Med Chir Soc Med Nat Iasi. 2008 Oct-Dec;112(4):1019-25
references.pmid: 20209780
references.citation: Blood. 2011 Mar 3;117(9):2625-39
references.pmid: 21148811
references.citation: Endocr Rev. 2006 Apr;27(2):141-69
references.pmid: 16434511
references.citation: Semin Nephrol. 2004 Nov;24(6):565-70
references.pmid: 15529291
references.citation: Am J Respir Crit Care Med. 2008 Apr 1;177(7):763-70
references.pmid: 18096709
references.citation: Annu Rev Pathol. 2010;5:173-92
references.pmid: 20078220
references.citation: Placenta. 2009 Mar;30 Suppl A:S32-7
references.pmid: 19070896
references.citation: J Clin Invest. 1996 Jan 15;97(2):540-50
references.pmid: 8567979
references.citation: Mol Cell Biol. 2003 May;23(10):3566-74
references.pmid: 12724415
references.citation: Reprod Biol Endocrinol. 2011 Aug 02;9:107
references.pmid: 21810232
references.citation: Eur J Immunol. 2003 Feb;33(2):567-77
references.pmid: 12645956
references.citation: Nat Rev Immunol. 2003 Jun;3(6):445-53
references.pmid: 12776204
references.citation: Mol Cell Endocrinol. 2005 Sep 28;241(1-2):73-9
references.pmid: 15955620
references.citation: J Immunol. 2000 May 15;164(10):4991-5
references.pmid: 10799849
references.citation: Placenta. 1991 Jul-Aug;12(4):301-8
references.pmid: 1946241
references.citation: Exp Cell Res. 1990 Feb;186(2):306-16
references.pmid: 2153559
references.citation: Reprod Biol Endocrinol. 2010 Oct 29;8:128
references.pmid: 21034435
references.citation: Placenta. 2009 Mar;30 Suppl A:S49-54
references.pmid: 19027159
references.citation: Science. 1997 Sep 12;277(5332):1669-72
references.pmid: 9287221
references.citation: Placenta. 2000 Mar-Apr;21 Suppl A:S25-30
references.pmid: 10831118
references.citation: Am J Obstet Gynecol. 1994 Jul;171(1):158-64
references.pmid: 8030692
references.citation: Placenta. 2007 May-Jun;28(5-6):399-407
references.pmid: 17098281
references.citation: Am J Reprod Immunol. 1997 Mar;37(3):240-9
references.pmid: 9127646
references.citation: Placenta. 1997 Sep;18(7):597-604
references.pmid: 9290157
references.citation: Reproduction. 2010 Nov;140(5):759-66
references.pmid: 20696850
references.citation: Endocrinology. 1986 Apr;118(4):1567-82
references.pmid: 3512258
references.citation: Biol Reprod. 2007 Feb;76(2):203-10
references.pmid: 17021346
references.citation: Placenta. 2000 Jan;21(1):73-8
references.pmid: 10692254
references.citation: Am J Hypertens. 2009 Jun;22(6):687-92
references.pmid: 19282816
references.citation: Am J Reprod Immunol. 2004 Sep;52(3):218-23
references.pmid: 15373762
references.citation: Biochim Biophys Acta. 2003 May 20;1638(1):63-71
references.pmid: 12757936
references.citation: Eur J Obstet Gynecol Reprod Biol. 2012 Dec;165(2):194-8
references.pmid: 22901903
references.citation: Placenta. 1981 Jul-Sep;2(3):193-204
references.pmid: 7279874
references.citation: Nat Immunol. 2006 Dec;7(12):1266-73
references.pmid: 17110943
references.citation: J Clin Invest. 2004 Sep;114(6):744-54
references.pmid: 15372095
references.citation: J Reprod Immunol. 2008 Jun;78(1):80-3
references.pmid: 18023484
references.citation: Biol Reprod. 2011 Jan;84(1):167-78
references.pmid: 20844277
references.citation: J Reprod Dev. 2013;59(1):7-13
references.pmid: 22986926
references.citation: J Soc Gynecol Investig. 2004 Sep;11(6):353-62
references.pmid: 15350247
references.citation: Placenta. 2004 Jul;25(6):479-88
references.pmid: 15135230
references.citation: Cell Death Differ. 2010 May;17(5):846-59
references.pmid: 19942931
references.citation: J Cell Physiol. 1996 Aug;168(2):346-53
references.pmid: 8707870
references.citation: Adv Exp Med Biol. 2011;713:81-95
references.pmid: 21432015