Abstract
Lactoferrin (LF) exhibits a wide range of immunomodulatory activities including modulation of cytokine and chemokine secretion. In this study, we demonstrate that bovine LF (bLF) up-modulates, in a concentration- and time-dependent manner, CCL1 secretion in monocytes (Mo) at the early stage of differentiation toward dendritic cells (DCs), and in fully differentiated immature Mo-derived DCs (MoDCs). In both cell types, up-modulation of CCL1 secretion is an early event following bLF-mediated enhanced accumulation of CCL1 transcripts. Notably, bLF-mediated up-regulation of CCL1 involves the engagement of distinct surface receptors in MoDCs and their Mo precursors. We show that bLF-mediated engagement of CD36 contributes to CCL1 induction in differentiating Mo. Conversely, toll-like receptor (TLR)2 blocking markedly reduces bLF-induced CCL1 production in MoDCs. These findings add further evidence for cell-specific differential responses elicited by bLF through the engagement of distinct TLRs and surface receptors. Furthermore, the different responses observed at early and late stages of Mo differentiation towards DCs may be relevant in mediating bLF effects in specific body districts, where these cell types may be differently represented in physiopathological conditions.
Highlights
Lactoferrin (LF) is an iron binding glycoprotein belonging to the transferrin family that is considered a major component of the mammal’s innate immune system
CC chemokine ligand 1 (CCL1) was still detected in the culture supernatant at the end of the culture period, when Mo treated with bovine LF (bLF) have fully differentiated into Mo-derived DCs (MoDCs), even upon medium replacement 18 h post bLF treatment (Figure 1C), indicating that CCL1 secretion is not a transient event but continues in spite of stimulus removal
LFisisnowadays nowadays recognized a first‐line defense protein that aplays a role critical role in the recognized as aasfirst-line defense protein that plays critical in the regulation regulation of immune response to infectious assault, trauma and injury, naturally bridging innate to of immune response to infectious assault, trauma and injury, naturally bridging innate to adaptive adaptive functions
Summary
Lactoferrin (LF) is an iron binding glycoprotein belonging to the transferrin family that is considered a major component of the mammal’s innate immune system. The role of LF in maintaining immune system homeostasis has not been fully elucidated, some regulatory activity may depend on its interaction with pathogen-associated molecular patterns and other surface receptors expressed on innate cells including monocytes (Mo), macrophages and dendritic cells (DCs) [5,6]. Mo continuously migrate from the blood into peripheral tissues where, in response to environmental stimuli, they differentiate into DCs [8] These latter cells are the most potent and versatile antigen-presenting cells (APCs) capable of inducing protective adaptive immune responses and tolerance to self-antigens. DCs (MoDCs) and their Mo precursors by distinct mechanisms involving the trans-membrane glycoprotein TLR2 and CD36 Overall, these cell-specific bLF-mediated effects may represent a strategy to elicit anti-inflammatory responses in specific body districts, where these cell types may be differently represented in physiopathological conditions
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