title: Macrophage migration inhibitory factor-nitric oxide interaction in human fetal membranes at term pregnancy.
abstract: OBJECTIVE
  Macrophage migration inhibitory factor (MIF), a multifunctional proinflammatory cytokine, has been recently involved in many aspects of reproduction including pregnancy. However, no evidence is available on the role of MIF in gestational tissues nor on factors regulating MIF production. This study, conducted on explants of human fetal membranes at term gestation, has been undertaken to investigate whether: (1) MIF is produced by fetal membranes; (2) nitric oxide (NO) can regulate local MIF production; and (3) MIF, in turn, can influence NO release in these tissues.
  
  
  METHODS
  Tissues were obtained from 56 healthy women who underwent elective cesarean delivery. Fetal membranes have been incubated with either sodium nitroprusside (NP), a NO donor, or recombinant MIF (r-MIF), or a specific anti-MIF antibody (MIF-Ab). Reverse transcriptase-polymerase chain reaction (RT-PCR), Western blot, enzyme-linked immunosorbent assay (ELISA), and colorimetric assay have been used to detect MIF mRNA and protein, inducible nitric oxide synthase (iNOS), and NO metabolites.
  
  
  RESULTS
  Fetal membranes basally express MIF mRNA and protein and release MIF. Exposing tissues to NP results in an increase of MIF mRNA expression and protein release. Conversely, treatment of tissues with MIF is followed by a reduction in iNOS mRNA and protein expression as well as in NO release. These effects are reversed by adding MIF-Ab.
  
  
  CONCLUSIONS
  MIF is generated and released by human fetal membranes at term. MIF mRNA and protein expression and release are modulated by NO. MIF, in turn, can reduce iNOS expression and NO release by these tissues. NO could be a regulator of MIF production in pregnancy and labor.
authors.affiliation: Department of Experimental Medicine and Pathology, University La Sapienza, Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Zicari
authors.forename: Carlo
authors.initials: C
authors.lastname: Ticconi
authors.forename: Francesca
authors.initials: F
authors.lastname: Ietta
authors.forename: Alessia
authors.initials: A
authors.lastname: Belmonte
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Bechi
authors.forename: Massimo
authors.initials: M
authors.lastname: Realacci
authors.forename: Maura
authors.initials: M
authors.lastname: Di Vito
authors.forename: Felice
authors.initials: F
authors.lastname: Arcuri
authors.forename: Matteo
authors.initials: M
authors.lastname: Russo
authors.forename: Emilio
authors.initials: E
authors.lastname: Piccione
authors.forename: Luana
authors.initials: L
authors.lastname: Paulesu
mesh_terms: D000906:Antibodies; D015153:Blotting, Western; D002478:Cells, Cultured; D005321:Extraembryonic Membranes / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008263:Macrophage Migration-Inhibitory Factors / Q000096:biosynthesis / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D011247:Pregnancy; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D047929:Term Birth
chemical_list: D000906:Antibodies; D008263:Macrophage Migration-Inhibitory Factors; D011994:Recombinant Proteins; D009569:Nitric Oxide