Lactoferrin differently modulates the inflammatory response in epithelial models mimicking human inflammatory and infectious diseases.
Conflicting data are reported on pro- or anti-inflammatory activity of bovine lactoferrin (bLf) in different cell models as phagocytes or epithelial cell lines infected by bacteria. Here we evaluated the bLf effect on epithelial models mimicking two human pathologies characterized by inflammation and infection with specific bacterial species. Primary bronchial epithelium from a cystic fibrosis (CF) patient and differentiated intestinal epithelial cells were infected with Pseudomonas aeruginosa LESB58 isolated from a CF patient and Adherent-Invasive Escherichia coli LF82 isolated from a Crohn's disease patient. Surprisingly, bLf significantly reduced the intracellular bacterial survival, but differently modulated the inflammatory response. These data lead us to hypothesize that bLf differentially acts depending on the epithelial model and infecting pathogen. To verify this hypothesis, we explored whether bLf could modulate ferroportin (Fpn), the only known cellular iron exporter from cells, that, by lowering the intracellular iron level, determines a non permissive environment for intracellular pathogens. Here, for the first time, we describe the bLf ability to up-regulate Fpn protein in infected epithelial models. Our data suggest that the mechanism underlying the bLf modulating activity on inflammatory response in epithelial cells is complex and the bLf involvement in modulating cellular iron homeostasis should be taken into account.
Microbiology Section, Department of Public Health and Infectious Diseases, University Sapienza of Rome, P.le A. Moro 5, 00185, Rome, Italy.
Alessandra
A
Frioni
Maria Pia
MP
Conte
Antimo
A
Cutone
Catia
C
Longhi
Giovanni
G
Musci
Maria Carmela Bonaccorsi
MC
di Patti
Tiziana
T
Natalizi
Massimiliano
M
Marazzato
Maria Stefania
MS
Lepanto
Patrizia
P
Puddu
Rosalba
R
Paesano
Piera
P
Valenti
Francesca
F
Berlutti
D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000276:immunology / Q000502:physiology; D001980:Bronchi / Q000382:microbiology / Q000473:pathology / Q000503:physiopathology; D027682:Cation Transport Proteins / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D003424:Crohn Disease / Q000382:microbiology / Q000473:pathology / Q000503:physiopathology; D003550:Cystic Fibrosis / Q000382:microbiology / Q000473:pathology / Q000503:physiopathology; D004847:Epithelial Cells / Q000382:microbiology / Q000473:pathology / Q000502:physiology; D004926:Escherichia coli / Q000472:pathogenicity; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology*; D007501:Iron / Q000378:metabolism; D007781:Lactoferrin / Q000008:administration & dosage / Q000276:immunology / Q000502:physiology*; D008954:Models, Biological; D011550:Pseudomonas aeruginosa / Q000472:pathogenicity; D020545:Respiratory Mucosa / Q000382:microbiology / Q000473:pathology / Q000503:physiopathology; D000098742:Ferroportin
D023181:Antimicrobial Cationic Peptides; D027682:Cation Transport Proteins; D018836:Inflammation Mediators; D000098742:Ferroportin; D007501:Iron; D007781:Lactoferrin