title: Lactoferrin works as a new LPS-binding protein in inflammatory activation of macrophages.
abstract: Though lactoferrin (LF) is a glycoprotein that is involved in immunomodulation, its action mechanism has not been fully elucidated. Previous studies have suggested that lipopolysaccharide (LPS) activity is inhibited by direct binding between LPS and LF. However, here we show that when LPS and purified LF was mixed, and formed a complex (termed as LF-LPS), it was found to induce production of inflammatory mediators in macrophages to some extent, rather than inhibit LPS activity. Moreover, when macrophages were pretreated with LF-LPS, cells were rendered a tolerant state to LPS challenge. These macrophage-activating effects were mediated by Toll-like receptor 4 (TLR4)-NF-kappaB pathway. Comparative studies with C3H/HeN and C3H/HeJ mice demonstrated the strong dependency of the LF-LPS signal on TLR4. These findings suggest that the immunomodulatory properties of LF could be due, in part, to LPS binding.
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Yuseong-gu, Daejeon 305-701, Republic of Korea.
authors.forename: Yong Joo
authors.initials: YJ
authors.lastname: Na
authors.forename: Sang Bae
authors.initials: SB
authors.lastname: Han
authors.forename: Jong Soon
authors.initials: JS
authors.lastname: Kang
authors.forename: Yeo Dae
authors.initials: YD
authors.lastname: Yoon
authors.forename: Song-Kyu
authors.initials: SK
authors.lastname: Park
authors.forename: Hwan Mook
authors.initials: HM
authors.lastname: Kim
authors.forename: Kyu-Hwan
authors.initials: KH
authors.lastname: Yang
authors.forename: Cheol O
authors.initials: CO
authors.lastname: Joe
mesh_terms: D000209:Acute-Phase Proteins / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000494:pharmacology*; D002478:Cells, Cultured; D024202:Electrophoretic Mobility Shift Assay; D007118:Immunoassay; D007249:Inflammation / Q000473:pathology*; D007781:Lactoferrin / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects*; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D008809:Mice, Inbred C3H; D016328:NF-kappa B / Q000378:metabolism; D009573:Nitrites / Q000032:analysis / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D000099231:Lipopolysaccharide-Binding Protein
chemical_list: D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D007781:Lactoferrin; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D009573:Nitrites; D011956:Receptors, Cell Surface; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D000099231:Lipopolysaccharide-Binding Protein