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Lactoferrin differently modulates the inflammatory response in epithelial models mimicking human inflammatory and infectious diseases

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Abstract

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.

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Acknowledgments

This work was granted by Italian Cystic Fibrosis Research Foundation (research project FFC#13/2013 adopted by Delegazione FFC di Palermo e di Vittoria Ragusa Catania 2) to FB and by Sapienza University of Rome to PV; thanks are due to Luigi Rosa for his enthusiastic technical assistance.

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Authors and Affiliations

  1. Microbiology Section, Department of Public Health and Infectious Diseases, University Sapienza of Rome, P.le A. Moro 5, 00185, Rome, Italy

    Alessandra Frioni, Maria Pia Conte, Antimo Cutone, Catia Longhi, Tiziana Natalizi, Massimiliano Marazzato, Maria Stefania Lepanto, Piera Valenti & Francesca Berlutti

  2. Department of Biosciences and Territory, University of Molise, c.da Fonte Lappone, Pesche, IS, Italy

    Giovanni Musci

  3. Department of Biochemical Sciences, Sapienza University, P.le A. Moro 5, 00185, Rome, Italy

    Maria Carmela Bonaccorsi di Patti

  4. Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161, Rome, Italy

    Patrizia Puddu

  5. Department of Women’s Health and Territorial Medicine, Sapienza University of Rome, P.le A. Moro 5, 00185, Rome, Italy

    Rosalba Paesano

Authors
  1. Alessandra Frioni
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  2. Maria Pia Conte
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  3. Antimo Cutone
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  4. Catia Longhi
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  5. Giovanni Musci
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  6. Maria Carmela Bonaccorsi di Patti
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  7. Tiziana Natalizi
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  8. Massimiliano Marazzato
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  9. Maria Stefania Lepanto
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  10. Patrizia Puddu
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  11. Rosalba Paesano
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  12. Piera Valenti
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  13. Francesca Berlutti
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Corresponding author

Correspondence to Francesca Berlutti.

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This paper is dedicated to the memory of our colleague, Dr. Patriza Puddu who recently passed away.

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Frioni, A., Conte, M.P., Cutone, A. et al. Lactoferrin differently modulates the inflammatory response in epithelial models mimicking human inflammatory and infectious diseases. Biometals 27, 843–856 (2014). https://doi.org/10.1007/s10534-014-9740-9

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  • DOI: https://doi.org/10.1007/s10534-014-9740-9

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