Functional Significance of the Binding of Lactoferrin to DNA

Furmanski, Philip; He, Julian; Li, Ying; Bezault, Joann; Bhimani, Ramesh; Ho, Kinfan

doi:10.1007/978-1-4612-3956-7_20

Cited by 4 publications

(2 citation statements)

References 42 publications

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“…1980; Ambruso & Johnston 1981; Nishiya & Horwitz 1982) and promote growth of Bifidobacterium (Kodama 1983). Although characterized by its very high avidity for Fe, Lf also binds to DNA (Bennett & Davis 1982), which can lead to transcriptional activation and may relate to the diverse regulatory effects of the molecule (He & Furmanski 1995; Furmanski et al . 1997).…”

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confidence: 99%

Influence of lactoferrin feeding and injection against systemic staphylococcal infections in mice

1999

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R .S . B H IM AN I , Y . V E ND RO V AN D P . FU RM A NS KI . 1999. Human and bovine lactoferrins (Lfs) and bovine lactoferrin hydrolysate (LH) were assessed in vitro and in vivo for their antibacterial effects on Staphylococcus aureus. Lactoferrins showed weak in vitro antibacterial activity while Fe-saturated Lfs and LH showed no activity. Lactoferrin-treated mice (1 mg, i.v.) when injected i.v. with 10 6 staphylococci, showed 30-50% reduction in kidney infections, and viable bacterial counts in the kidneys decreased 5-12-fold. The inhibitory effect was dosedependent up to 1 mg Lf. Lactoferrins were effective when given 1 day prior to the bacterial challenge, after which there was no significant effect even at doses up to 5 mg. Apo-and Fesaturated forms of human and bovine Lfs were all equally effective, while LH was not protective. Human and bovine Lfs with different degrees of iron saturation (9-97%) were found to be equipotent. Feeding mice with 2% bLf in drinking water also reduced the kidney infections by 40-60%, and viable bacterial counts, 5-12-fold. The results suggest a potential for the use of Lfs as natural antibacterial proteins for preventing bacterial infections.

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confidence: 99%

Influence of lactoferrin feeding and injection against systemic staphylococcal infections in mice

1999

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“…On the other hand, LF binds to specific DNA sequences and this interaction leads to transcriptional activation. 117 Therefore, some LF-mediated effects at the cellular level may depend, at least in part, on its involvement in communication, signalling, and regulation of gene expression.…”

Section: Immunoregulatory Functions and Effects On Inflammationmentioning

confidence: 99%

Review: Antimicrobial and immunoregulatory functions of lactoferrin and its potential therapeutic application

Caccavo

Pellegrino

Altamura

et al. 2002

Journal of Endotoxin Research

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Lactoferrin is an iron-binding glycoprotein present in various secretions (eg. milk, tears, saliva,pancreatic juice, etc.). It is also stored in specific granules of polymorphonuclear granulocytes from which it is released following activation. Lactoferrin exerts a bactericidal activity by damaging the outermembrane of Gram-negative bacteria, as well as immunoregulatory functions by decreasing the release of interleukin-l (IL- 1), IL-2 and tumor necrosis factor-alpha INF-alpha) and enhancing monocyte and natural killer cell cytotoxicity. Lactoferrin binds with high affinity to lipid A, the toxic moiety of the lipopolysaccharide, or endotoxin from Gram-negative bacteria Lipopolysacchride interaction with monocytes/ma phages results in the production and release of TNF-alpha, that plays an important role in inducing septic shock In this respect, it has recently been demonstrated that lactoferrin inhibits the lipopolysaccharide interaction with CD14 on monocytes/macrophages by competition with the lipopolysaccharide binding protein. Therefore, besides its bactericidal activity, lactoferrin may also act by neutralizing the toxic effects of lipopolysaccharide and this protective role against endotoxin lethal shock has been demonstrated in animal models. Moreover, in vitro and in vivo neutralization of endotoxin by a human lactoferrin-derived peptide was also reported and lactoferrin or lactoferrin-derived peptides could represent useful tools for the treatment of endotoxin-induced septic hock. The recent production and characterization of monoclonal antibodies against different epitopes of human lactoferrin, including monoclonal antibodies selectively neutralizing lactoferrin binding to lipid A, may allow a better elucidation of the consequence of lactoferrin-lipopolysaccharide interaction.

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Downregulation of Lactoferrin by PPARalpha Ligands: Role in Perturbation of Hepatocyte Proliferation and Apoptosis

Hasmall

Orphanides²,

James³

et al. 2002

Toxicological Sciences

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PPARalpha (peroxisome proliferator activated receptor alpha) is a transcription factor that mediates the rodent liver tumorigenic responses to peroxisome proliferators via regulation of genes that remain to be identified. Using microarray gene expression profiling of mRNA from wild type versus PPARalpha null mice, we detected a 3- to 7-fold downregulation of hepatic lactoferrin (LF) in response to the PP, diethylhexylphthalate (DEHP; 1150 mg/kg). Northern blot analyses confirmed a significant downregulation of LF mRNA by DEHP in wild type mouse liver. Since LF has been reported to repress tumor necrosis factor-alpha (TNF-alpha), LF downregulation by PPs may permit TNF-alpha levels to rise, enhancing hepatocyte survival and proliferation. To test this hypothesis, we asked if exogenous LF could prevent the perturbation of hepatocyte growth by PPs but not by TNF-alpha. In vitro, the PPs monoethylhexylphthalate (MEHP; 500 microM, the active metabolite of DEHP) and another PP, nafenopin (50 microM) or exogenous TNF-alpha (5000 U/ml) induced hepatocyte proliferation and suppressed apoptosis. LF (200 microM) blocked the growth but not the peroxisome proliferation response to PPs but could not block the growth response to TNF-alpha. Immunocytochemistry using specific antibodies to LF but also to transferrin (TF), a related gene previously shown to contain a PP response element (PPRE), demonstrated that both LF and TF are expressed in murine liver. Furthermore, both were downregulated by DEHP in both wild type and PPARalpha null mouse liver. These data suggest that the regulation of iron binding proteins by PPARalpha ligands plays a role in PP-mediated liver growth, but not in peroxisome proliferation.

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Functional Significance of the Binding of Lactoferrin to DNA

Cited by 4 publications

References 42 publications

Influence of lactoferrin feeding and injection against systemic staphylococcal infections in mice

Influence of lactoferrin feeding and injection against systemic staphylococcal infections in mice

Review: Antimicrobial and immunoregulatory functions of lactoferrin and its potential therapeutic application

Downregulation of Lactoferrin by PPARalpha Ligands: Role in Perturbation of Hepatocyte Proliferation and Apoptosis

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