TY - JOUR
T1 - Recombinant human lactoferrin induces human and mouse dendritic cell maturation via Toll-like receptors 2 and 4
AU - Spadaro, Michela
AU - Montone, Monica
AU - Arigoni, Maddalena
AU - Cantarella, Daniela
AU - Forni, Guido
AU - Pericle, Federica
AU - Pascolo, Steve
AU - Calogero, Raffaele A.
AU - Cavallo, Federica
PY - 2014
Y1 - 2014
N2 - Lactoferrin, a key component of innate immunity, is a cationic monomeric 80-kDa glycoprotein of the transferrin superfamily. Recombinant human lactoferrin, known as talactoferrin (TLF), induces a distinct functional maturation program in human dendritic cells (DCs) derived from peripheral blood monocytes. However, the receptors and molecular mechanisms involved in this induction have not been fully determined. By exploiting genome-wide transcription profiling of immature DCs, TNF-α- and IL-1β-matured DCs (m-DCs), and TLF-matured DCs (TLF-DCs), we have detected a set of transcripts specific for m-DCs and one specific for TLF-DCs. Functional network reconstruction highlighted, as expected, the association of m-DC maturation with IL-1β, TNF-α, and NF-κB, whereas TLF-DC maturation was associated with ERK and NF-κB. This involvement of ERK and NF-κB transduction factors suggests direct involvement of Toll-like receptors (TLRs) in TLF-induced maturation. We have used MyD88 inhibition and siRNA silencing TLRs on human DCs and mouse TLR-2-knockout cells, to show that TLF triggers the maturation of both human and mouse DCs through TLR-2 and TLR-4.
AB - Lactoferrin, a key component of innate immunity, is a cationic monomeric 80-kDa glycoprotein of the transferrin superfamily. Recombinant human lactoferrin, known as talactoferrin (TLF), induces a distinct functional maturation program in human dendritic cells (DCs) derived from peripheral blood monocytes. However, the receptors and molecular mechanisms involved in this induction have not been fully determined. By exploiting genome-wide transcription profiling of immature DCs, TNF-α- and IL-1β-matured DCs (m-DCs), and TLF-matured DCs (TLF-DCs), we have detected a set of transcripts specific for m-DCs and one specific for TLF-DCs. Functional network reconstruction highlighted, as expected, the association of m-DC maturation with IL-1β, TNF-α, and NF-κB, whereas TLF-DC maturation was associated with ERK and NF-κB. This involvement of ERK and NF-κB transduction factors suggests direct involvement of Toll-like receptors (TLRs) in TLF-induced maturation. We have used MyD88 inhibition and siRNA silencing TLRs on human DCs and mouse TLR-2-knockout cells, to show that TLF triggers the maturation of both human and mouse DCs through TLR-2 and TLR-4.
KW - Alarmins
KW - Pattern recognition receptors
UR - http://www.scopus.com/inward/record.url?scp=84894555299&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84894555299&partnerID=8YFLogxK
U2 - 10.1096/fj.13-229591
DO - 10.1096/fj.13-229591
M3 - Article
C2 - 24088817
AN - SCOPUS:84894555299
VL - 28
SP - 416
EP - 429
JO - FASEB Journal
JF - FASEB Journal
SN - 0892-6638
IS - 1
ER -