title: Bovine Lactoferrin-Induced CCL1 Expression Involves Distinct Receptors in Monocyte-Derived Dendritic Cells and Their Monocyte Precursors.
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.
authors.affiliation: Istituto Superiore di Sanità, Department of Hematology, Oncology and Molecular Medicine, Viale Regina Elena 299, Rome 00161, Italy. daniela.latorre@irb.usi.ch.
authors.forename: Daniela
authors.initials: D
authors.lastname: Latorre
authors.affiliation: Istituto Superiore di Sanità, Department of Hematology, Oncology and Molecular Medicine, Viale Regina Elena 299, Rome 00161, Italy. nadia.pulvirenti@gmail.com.
authors.forename: Nadia
authors.initials: N
authors.lastname: Pulvirenti
authors.affiliation: Istituto Superiore di Sanità, Department of Hematology, Oncology and Molecular Medicine, Viale Regina Elena 299, Rome 00161, Italy. daniela.covino@iss.it.
authors.forename: Daniela Angela
authors.initials: DA
authors.lastname: Covino
authors.affiliation: Istituto Superiore di Sanità, Department of Hematology, Oncology and Molecular Medicine, Viale Regina Elena 299, Rome 00161, Italy. barbara.varano@iss.it.
authors.forename: Barbara
authors.initials: B
authors.lastname: Varano
authors.affiliation: Istituto Superiore di Sanità, Department of Hematology, Oncology and Molecular Medicine, Viale Regina Elena 299, Rome 00161, Italy. cristina.purificato@iss.it.
authors.forename: Cristina
authors.initials: C
authors.lastname: Purificato
authors.affiliation: Istituto Superiore di Sanità, Department of Hematology, Oncology and Molecular Medicine, Viale Regina Elena 299, Rome 00161, Italy. gabriella.rainaldi@iss.it.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Rainaldi
authors.affiliation: Istituto Superiore di Sanità, Department of Hematology, Oncology and Molecular Medicine, Viale Regina Elena 299, Rome 00161, Italy. mariacristina.gauzzi@iss.it.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Gauzzi
authors.affiliation: Istituto Superiore di Sanità, Department of Hematology, Oncology and Molecular Medicine, Viale Regina Elena 299, Rome 00161, Italy. laura.fantuzzi@iss.it.
authors.forename: Laura
authors.initials: L
authors.lastname: Fantuzzi
authors.affiliation: Istituto Superiore di Sanità, Department of Hematology, Oncology and Molecular Medicine, Viale Regina Elena 299, Rome 00161, Italy. lucia.conti@iss.it.
authors.forename: Lucia
authors.initials: L
authors.lastname: Conti
authors.affiliation: Istituto Superiore di Sanità, Department of Hematology, Oncology and Molecular Medicine, Viale Regina Elena 299, Rome 00161, Italy. gloria.donninnelli@iss.it.
authors.forename: Gloria
authors.initials: G
authors.lastname: Donninelli
authors.affiliation: Istituto Superiore di Sanità, Department of Hematology, Oncology and Molecular Medicine, Viale Regina Elena 299, Rome 00161, Italy. manuela.delcorno@iss.it.
authors.forename: Manuela
authors.initials: M
authors.lastname: Del Cornò
authors.affiliation: Istituto Superiore di Sanità, Department of Hematology, Oncology and Molecular Medicine, Viale Regina Elena 299, Rome 00161, Italy. michela.sabbatucci@iss.it.
authors.forename: Michela
authors.initials: M
authors.lastname: Sabbatucci
authors.affiliation: Istituto Superiore di Sanità, Department of Hematology, Oncology and Molecular Medicine, Viale Regina Elena 299, Rome 00161, Italy. sandra.gessani@iss.it.
authors.forename: Sandra
authors.initials: S
authors.lastname: Gessani
authors.affiliation: Istituto Superiore di Sanità, Department of Hematology, Oncology and Molecular Medicine, Viale Regina Elena 299, Rome 00161, Italy. patrizia.puddu@iss.it.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Puddu
mesh_terms: D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D054402:Chemokine CCL1 / Q000235:genetics / Q000378:metabolism*; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007781:Lactoferrin / Q000494:pharmacology*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: C065971:CCL1 protein, human; D054402:Chemokine CCL1; D012333:RNA, Messenger; D007781:Lactoferrin
keywords: CCL1; dendritic cell; lactoferrin; monocyte; surface receptors