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BioMetals

, Volume 31, Issue 3, pp 369–379 | Cite as

Role of lactoferrin and its receptors on biliary epithelium

  • Romina Mancinelli
  • Francesca Olivero
  • Guido Carpino
  • Diletta Overi
  • Luigi Rosa
  • Maria Stefania Lepanto
  • Antimo Cutone
  • Antonio Franchitto
  • Gianfranco Alpini
  • Paolo Onori
  • Piera Valenti
  • Eugenio Gaudio
Article

Abstract

Human lactoferrin is an iron-binding glycoprotein present at high concentrations in breast milk and colostrum. It is produced by many exocrine glands and widely distributed in a variety of body fluids. This protein has antimicrobial, immunomodulatory, antioxidant, and anticancer properties. Two important hLf receptors have been identified: LDL receptor related protein (LRP1), a low specificity receptor, and intelectin-1 (ITLN1), a high specificity receptor. No data are present on the role of hLf on the biliary epithelium. Our aims have been to evaluate the expression of Lf and its receptors in human and murine cholangiocytes and its effect on proliferation. Immunohistochemistry and immunofluorescence (IF) were conducted on human healthy and primary biliary cholangitis (PBC) liver samples as well as on liver samples obtained from normal and bile duct ligated (BDL) mice to evaluate the expression of Lf, LRP1 and ITLN1. Cell proliferation in vitro studies were performed on human cholangiocyte cell lines via 3-(4,5-dimetiltiazol-2-il)-2,5-diphenyltetrazolium assay as well as IF to evaluate proliferating cell nuclear antigen (PCNA) expression. Our results show that mouse and human cholangiocytes express Lf, LRP1 and ITLN1, at higher extent in cholangiocytes from BDL and PBC samples. Furthermore, the in vitro addition of bovine Lf (bLf) has a proliferative effect on human cholangiocyte cell line. The results support a proliferative role of hLf on the biliary epithelium; this pro-proliferative effect of hLf and bLf on cholangiocytes could be particularly relevant in human cholangiopathies such as PBC, characterized by cholangiocyte death and ductopenia.

Keywords

Biliary epithelium Cholangiocytes Lactoferrin Intelectin-1 Primary biliary cholangitis 

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Romina Mancinelli
    • 1
  • Francesca Olivero
    • 1
  • Guido Carpino
    • 3
  • Diletta Overi
    • 1
  • Luigi Rosa
    • 2
  • Maria Stefania Lepanto
    • 2
  • Antimo Cutone
    • 2
  • Antonio Franchitto
    • 1
  • Gianfranco Alpini
    • 4
  • Paolo Onori
    • 1
  • Piera Valenti
    • 2
  • Eugenio Gaudio
    • 1
  1. 1.Department of Anatomical, Histological, Forensic and Orthopedic SciencesSapienza University of RomeRomeItaly
  2. 2.Department of Public Health and Infectious DiseasesSapienza University of RomeRomeItaly
  3. 3.Department of Movement, Human and Health SciencesSapienza University of RomeRomeItaly
  4. 4.Research, Central Texas Veterans Health Care System, Baylor Scott & White Digestive Disease Research Center, Baylor Scott & White, Department of Medical PhysiologyTexas A&M University College of MedicineTempleUSA

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