title: Vaginal Lactoferrin Modulates PGE2, MMP-9, MMP-2, and TIMP-1 Amniotic Fluid Concentrations.
abstract: Inflammation plays an important role in pregnancy, and cytokine and matrix metalloproteases (MMPs) imbalance has been associated with premature rupture of membranes and increased risk of preterm delivery. Previous studies have demonstrated that lactoferrin (LF), an iron-binding protein with anti-inflammatory properties, is able to decrease amniotic fluid (AF) levels of IL-6. Therefore, we aimed to evaluate the effect of vaginal LF administration on amniotic fluid PGE2level and MMP-TIMP system in women undergoing genetic amniocentesis. One hundred and eleven women were randomly divided into controls (n= 57) or treated with LF 4 hours before amniocentesis (n= 54). Amniotic fluid PGE2, active MMP-9 and MMP-2, and TIMP-1 and TIMP-2 concentrations were determined by commercially available assays and the values were normalized by AF creatinine concentration. PGE2, active MMP-9, and its inhibitor TIMP-1 were lower in LF-treated group than in controls (p< 0.01,p< 0.005, andp< 0.001, resp.). Conversely, active MMP-2 (p< 0.0001) and MMP-2/TIMP-2 molar ratio (p< 0.001) were increased, whilst TIMP-2 was unchanged. Our data suggest that LF administration is able to modulate the inflammatory response following amniocentesis, which may counteract cytokine and prostanoid imbalance that leads to abortion. This trial is registered with Clinical Trial number NCT02695563.
authors.affiliation: Section of Medical Biochemistry, Molecular Biology and Genetics, Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, 44121 Ferrara, Italy.
authors.forename: Alessandro
authors.identifier: 0000-0003-3579-7921
authors.initials: A
authors.lastname: Trentini
authors.affiliation: Section of Dermatology and Infectious Diseases, Department of Medical Sciences, University of Ferrara, 44121 Ferrara, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Maritati
authors.affiliation: Section of Medical Biochemistry, Molecular Biology and Genetics, Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, 44121 Ferrara, Italy.
authors.forename: Carlo
authors.identifier: 0000-0003-4777-6300
authors.initials: C
authors.lastname: Cervellati
authors.affiliation: Section of Medical Biochemistry, Molecular Biology and Genetics, Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, 44121 Ferrara, Italy.
authors.forename: Maria C
authors.identifier: 0000-0003-0174-539X
authors.initials: MC
authors.lastname: Manfrinato
authors.affiliation: Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, 44121 Ferrara, Italy.
authors.forename: Arianna
authors.initials: A
authors.lastname: Gonelli
authors.affiliation: Section of Orthopedics, Obstetrics and Gynecology and Anesthesia and Resuscitation, Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, 44121 Ferrara, Italy.
authors.forename: Carlo A
authors.identifier: 0000-0003-3533-6121
authors.initials: CA
authors.lastname: Volta
authors.affiliation: Section of Dermatology and Infectious Diseases, Department of Medical Sciences, University of Ferrara, 44121 Ferrara, Italy.
authors.forename: Fortunato
authors.identifier: 0000-0002-7083-5527
authors.initials: F
authors.lastname: Vesce
authors.affiliation: Section of Orthopedics, Obstetrics and Gynecology and Anesthesia and Resuscitation, Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, 44121 Ferrara, Italy.
authors.forename: Pantaleo
authors.initials: P
authors.lastname: Greco
authors.affiliation: Section of Medical Biochemistry, Molecular Biology and Genetics, Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, 44121 Ferrara, Italy.
authors.forename: Franco
authors.identifier: 0000-0002-5325-8377
authors.initials: F
authors.lastname: Dallocchio
authors.affiliation: Section of Medical Biochemistry, Molecular Biology and Genetics, Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, 44121 Ferrara, Italy.
authors.forename: Tiziana
authors.identifier: 0000-0001-7975-921X
authors.initials: T
authors.lastname: Bellini
authors.affiliation: Section of Dermatology and Infectious Diseases, Department of Medical Sciences, University of Ferrara, 44121 Ferrara, Italy.
authors.forename: Carlo
authors.identifier: 0000-0001-8809-6470
authors.initials: C
authors.lastname: Contini
mesh_terms: D000022:Abortion, Spontaneous / Q000517:prevention & control; D000328:Adult; D000649:Amniocentesis; D000653:Amniotic Fluid / Q000378:metabolism*; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D016207:Cytokines / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism*; D005260:Female; D006801:Humans; D007249:Inflammation; D007781:Lactoferrin / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D011247:Pregnancy; D012306:Risk; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*; D014621:Vagina / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; C490098:LTF protein, human; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D007781:Lactoferrin; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D015232:Dinoprostone