title: The first trimester gravid serum regulates procalcitonin expression in human macrophages skewing their phenotype in vitro.
abstract: Procalcitonin (PCT) is one of the best diagnostic and prognostic markers in clinical practice, widely used to evaluate the evolution of bacterial infections. Although it is mainly produced by thyroid, during sepsis almost all the peripheral tissues are involved in PCT production. Parenchymal cells have been suggested as the main source of PCT expression; however the contribution of macrophages is not clear yet. In response to environmental cues, tissue macrophages acquire distinct functional phenotypes, ranging from proinflammatory (M1) to anti-inflammatory (M2) phenotype. Macrophages at the fetal-maternal interface show immunosuppressive M2-like activities required for the maintenance of immunological homeostasis during pregnancy. This study aims to clarify the ability to synthesise PCT of fully differentiated (M0), polarized (M1/M2) macrophages and those cultured either in the presence of first trimester gravid serum (GS) or pregnancy hormones. We found out that M1 macrophages upregulate PCT expression following LPS stimulation compared to M0 and M2. The GS downregulates PCT expression in macrophages, skewing them towards an M2-like phenotype. This effect seems only partially mediated by the hormonal milieu. Our findings strengthen the key role of macrophages in counteracting inflammatory stimuli during pregnancy, suggesting PCT as a possible new marker of M1-like macrophages.
authors.affiliation: Department of Life Sciences, University of Trieste, Via Valerio 28, 34127 Trieste, Italy.
authors.forename: Damiano
authors.identifier: 0000-0001-9369-7422
authors.initials: D
authors.lastname: Rami
authors.affiliation: Department of Life Sciences, University of Trieste, Via Valerio 28, 34127 Trieste, Italy.
authors.forename: Martina
authors.identifier: 0000-0003-2759-9028
authors.initials: M
authors.lastname: La Bianca
authors.affiliation: Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", 34137 Trieste, Italy.
authors.forename: Chiara
authors.identifier: 0000-0002-8315-2258
authors.initials: C
authors.lastname: Agostinis
authors.affiliation: Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", 34137 Trieste, Italy.
authors.forename: Giorgio
authors.identifier: 0000-0002-3750-8698
authors.initials: G
authors.lastname: Zauli
authors.affiliation: Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", 34137 Trieste, Italy.
authors.forename: Oriano
authors.initials: O
authors.lastname: Radillo
authors.affiliation: Department of Life Sciences, University of Trieste, Via Valerio 28, 34127 Trieste, Italy.
authors.forename: Roberta
authors.identifier: 0000-0003-1737-5776
authors.initials: R
authors.lastname: Bulla
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002116:Calcitonin / Q000097:blood*; D015740:Calcitonin Gene-Related Peptide; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006706:Homeostasis; D006801:Humans; D007249:Inflammation; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism; D009000:Monocytes / Q000166:cytology; D010641:Phenotype; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011498:Protein Precursors / Q000097:blood*; D044967:Serum / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; C000606589:CALCA protein, human; D006063:Chorionic Gonadotropin; D011498:Protein Precursors; D004958:Estradiol; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide
references.citation: J Clin Endocrinol Metab. 1994 Dec;79(6):1605-8
references.pmid: 7989463
references.citation: Scand J Immunol. 2005 Feb;61(2):180-6
references.pmid: 15683455
references.citation: Nat Rev Immunol. 2010 Jun;10(6):453-60
references.pmid: 20467425
references.citation: Clin Infect Dis. 2011 May;52 Suppl 4:S346-50
references.pmid: 21460294
references.citation: Reprod Sci. 2010 Mar;17(3):209-18
references.pmid: 20065301
references.citation: BMC Microbiol. 2012 May 08;12:68
references.pmid: 22568957
references.citation: J Clin Endocrinol Metab. 2001 Jan;86(1):396-404
references.pmid: 11232031
references.citation: J Immunol Methods. 2012 Jan 31;375(1-2):196-206
references.pmid: 22075274
references.citation: Mol Immunol. 2008 May;45(9):2629-40
references.pmid: 18295334
references.citation: J Immunol. 2010 Jul 1;185(1):642-52
references.pmid: 20530259
references.citation: Front Immunol. 2012 Mar 19;3:55
references.pmid: 22566936
references.citation: J Reprod Immunol. 2013 Sep;99(1-2):62-8
references.pmid: 23958292
references.citation: Inflamm Res. 2012 May;61(5):401-9
references.pmid: 22354317
references.citation: Br J Pharmacol. 2010 Jan 1;159(2):253-64
references.pmid: 20002097
references.citation: Am J Reprod Immunol. 2010 Jun;63(6):425-33
references.pmid: 20367629
references.citation: Immunity. 2005 Oct;23(4):344-6
references.pmid: 16226499
references.citation: J Lab Clin Med. 1999 Jul;134(1):49-55
references.pmid: 10402059
references.citation: Immunol Lett. 2002 Dec 3;84(3):199-203
references.pmid: 12413737
references.citation: Nature. 1983 Jul 14-20;304(5922):129-35
references.pmid: 6346105
references.citation: J Immunol. 2011 Oct 1;187(7):3671-82
references.pmid: 21890660
references.citation: Nat Rev Immunol. 2009 Apr;9(4):259-70
references.pmid: 19282852
references.citation: J Clin Microbiol. 2010 Jul;48(7):2325-9
references.pmid: 20421436
references.citation: Endocrinology. 2003 Dec;144(12):5578-84
references.pmid: 12960010
references.citation: Shock. 2001 Aug;16(2):109-12
references.pmid: 11508861
references.citation: Cell Immunol. 2013 May-Jun;283(1-2):70-4
references.pmid: 23880295
references.citation: Eur J Immunol. 2007 Jan;37(1):14-6
references.pmid: 17183610
references.citation: Clin Exp Immunol. 2011 May;164(2):180-92
references.pmid: 21352205
references.citation: J Clin Invest. 2012 Mar;122(3):787-95
references.pmid: 22378047
references.citation: Crit Care Med. 2004 Aug;32(8):1715-21
references.pmid: 15286549