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Role of endogenous interferon and LPS in the immunomodulatory effects of bovine lactoferrin in murine peritoneal macrophages
Authors
Appelmelk
Baveye
+44 more
Baveye
Beignon
Belardelli
Belardelli
Beutler
Biron
Brandenburg
Curran
Di Marzio
Elass
Filippo Belardelli
Gessani
Gessani
Goodbourn
Gresser
Gresser
Hoshino
Ishikado
Jacobsen
Kruzel
Kuhara
Lee
Legrand
Legrand
Lichty
Livak
Machnicki
Maria Grazia Carollo
Mogensen
Morrison
Na
Patrizia Puddu
Piera Valenti
Proietti
Puddu
Qureshi
Sandra Gessani
Schiavoni
Sorimachi
Valenti
Van Berkel
Wakabayashi
Wang
Zagulski
Publication date
1 January 2007
Publisher
'Society for Leukocyte Biology'
Doi
Cite
Abstract
Lactoferrin (Lf) plays an important role in host defense against infection and excessive inflammation. Although the mechanisms underlying its immunomodulatory properties have not been fully elucidated yet, recent evidence suggests that some of these effects may be related to its capacity to form complexes with LPS. We report that the culture of resting mouse peritoneal macrophages (PM) with bovine Lf (bLf), prior to infection with the vesicular stomatitis virus (VSV), resulted in a significant reduction of virus yield with respect to control cultures. The antiviral activity of bLF was related to its capacity of inducing IFN-α/β expression, which in turn inhibited VSV replication. Indeed, the accumulation of IFN-β but not of IFNα 1-2 transcripts was up-modulated markedly early after bLf addition. Furthermore, bLf did not exert any antiviral activity in the presence of neutralizing antibodies to IFN-α/β in PM from wildtype mice, as well as in PM from mice genetically defective for the response to IFN. The antiviral activity of bLf relied on its intrinsic capacity to bind LPS, as this protein did not induce IFN expression in PM from LPS-hyporesponsive mice. It is interesting that this LPS-binding property was dispensable for the production of TNF-α, which also occurred in LPS-hyporesponsive mice. Overall, these results indicate that some of the immunomodulatory effects ascribed to Lf may be related to its capacity to favor Type I IFN expression and argue in favor of an important role of the LPS-binding feature and TLR4 in some of the effects ascribed to this molecule. © Society for Leukocyte Biology
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Last time updated on 05/06/2019
Archivio della ricerca- Università di Roma La Sapienza
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Last time updated on 12/11/2016