Bovine lactoferrin induces CCL1 production in myeloid cells
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1
Institute for Research in Biomedicine, Switzerland
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2
Istituto Superiore di Sanità, Immunoregulation Section Department of Hematology, Oncology and Molecular Medicine, Italy
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3
Department of Public Health Sciences and Infectious Diseases, Sapienza University of Rome, Italy
Lactoferrin (LF) is now recognized as a key element in mammalian immune system for its pivotal role in host defence against infection and excessive inflammation.
We previously demonstrated that bovine LF (bLF) exerts a potent anti-inflammatory activity by skewing monocyte differentiation into monocyte-derived dendritic cells (MD-DCs) with impaired capacity to undergo activation and to promote Th1 responses.
In this study we show that the exposure of both MD-DCs and their monocyte precursors to bLF induces CCL1 production, even though with differences in the protein amount. Interestingly, in freshly isolated monocytes CCL1 mRNA expression levels are significantly enhanced at 2 hours and more markedly at 4 hours after bLf-treatment, suggesting a direct role of bLF on CCL1 mRNA transcriptional activation. Furthermore, cells continue to produce this chemokine even upon medium replacement 18 hours post bLF-treatment indicating CCL1 production as a result of permanent changes induced in bLF-treated DC precursor cells.
The analysis of the role of TLR2 and TLR4, and their co-receptors CD14 and CD36, on bLF-mediated CCL1 production, indicates that blocking each of these receptors significantly influences soluble factor secretion with cell-specific differences.
Finally, CCL1 is not implicated in the bLF-mediated inhibition of MD-DCs activation since blocking its biological activity does not rescue their LPS-mediated up-modulation of CD83 and IL-12 production, as well as their ability to induce T cell proliferation.
Understanding the biological role of the bLF-induced CCL1 production in both monocytes and MD-DCs could provide further evidence for mechanisms underlying LF immunomodulatory activity.
Keywords:
dendritc cells,
Lactoferrin,
CCL1,
Myeloid Cells,
innate immunity,
Immunomodulation
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Innate immunity
Citation:
Latorre
D,
Puddu
P,
Gessani
S and
Valenti
P
(2013). Bovine lactoferrin induces CCL1 production in myeloid cells.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00569
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Received:
06 Jun 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Daniela Latorre, Institute for Research in Biomedicine, Bellinzona, Switzerland, latorred@biol.ethz.ch