title: Lactoferrin prevents invasion and inflammatory response following E. coli strain LF82 infection in experimental model of Crohn's disease.
abstract: BACKGROUND
  Crohn's disease is a multifactorial disease in which an aberrant immune response to commensal intestinal microbiota leads to chronic inflammation. The small intestine of patients with Crohn's disease is colonized by a group of adherent-invasive Escherichia coli strongly able to adhere and invade intestinal epithelial cells lactoferrin is an iron-binding glycoprotein known to have anti-bacterial and anti-inflammatory activities.
  
  
  OBJECTIVE
  We explore the ability of bovine lactoferrin to modulate the interactions between the adherent-invasive E. coli strain LF82 and intestinal epithelial cells as well as the inflammatory response.
  
  
  METHODS
  Bacterial adhesion and invasion assays were used to assess the antimicrobial activity of lactoferrin. Electron microscopy was used to characterize bacteria-cell interactions. The mRNA expression of pro-inflammatory cytokines was measured both in cultured cells and in biopsies taken from intestine of patients affected by Crohn's disease.
  
  
  RESULTS
  Lactoferrin inhibited bacterial invasion through minimally affecting adhesion. This divergence was due to a mannose-dependent lactoferrin binding to the bacterial type 1 pili and consequent bacterial aggregation on the intestinal epithelial cell surface. Expression of pro-inflammatory cytokines, such as TNF-alpha, IL-8, and IL-6, was markedly inhibited by lactoferrin both in cultured and Crohn-derived intestinal cells.
  
  
  CONCLUSIONS
  Bovine lactoferrin might function via an antibacterial and/or anti-inflammatory mechanism in the treatment of Crohn's disease.
authors.affiliation: Department of Technology and Health, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Bertuccini
authors.affiliation: ENEA, Italian National Agency for New Technologies, Energy and Sustainable Economic Development, Department of Radiobiology and Human Health, Via Anguillarese 301, 00123 Rome, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Costanzo
authors.affiliation: Department of Technology and Health, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Iosi
authors.affiliation: Department of Technology and Health, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Tinari
authors.affiliation: Giellepi S.p.A., Via G. Verdi, 41/Q, 20831 Seregno (MB), Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Terruzzi
authors.affiliation: ENEA, Italian National Agency for New Technologies, Energy and Sustainable Economic Development, Department of Radiobiology and Human Health, Via Anguillarese 301, 00123 Rome, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Stronati
authors.affiliation: Department of Pediatrics, Sapienza University of Rome, Viale Regina Elena, 324, 00161 Rome, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Aloi
authors.affiliation: Department of Pediatrics, Sapienza University of Rome, Viale Regina Elena, 324, 00161 Rome, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cucchiara
authors.affiliation: Department of Technology and Health, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy. Electronic address: fabiana.superti@iss.it.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Superti
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001422:Bacterial Adhesion / Q000187:drug effects*; D018938:Caco-2 Cells; D002417:Cattle; D003424:Crohn Disease / Q000276:immunology / Q000382:microbiology*; D004926:Escherichia coli / Q000187:drug effects* / Q000502:physiology; D004927:Escherichia coli Infections / Q000382:microbiology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D015850:Interleukin-6 / Q000235:genetics; D016209:Interleukin-8 / Q000235:genetics; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D007781:Lactoferrin / Q000494:pharmacology*; D008358:Mannose / Q000494:pharmacology; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D012333:RNA, Messenger / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D000890:Anti-Infective Agents; D015850:Interleukin-6; D016209:Interleukin-8; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha; C076610:fimbriae receptor, type 1; D007371:Interferon-gamma; D007781:Lactoferrin; D008358:Mannose
keywords: Adherent-invasive Escherichia coli; Bovine lactoferrin; Crohn's disease; Inflammatory bowel diseases