Direct effects of polymyxin B on human dendritic cells maturation. The role of IkappaB-alpha/NF-kappaB and ERK1/2 pathways and adhesion

Polymyxin B is a lipopolysaccharide binding antibiotic used to inactivate potential lipopolysaccharide contaminations when evaluating the activity of different agents on innate immune cells. We report that polymyxin B is able to induce directly in monocyte-derived human dendritic cells (DCs) several...

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Bibliographic Details
Published in:The Journal of biological chemistry Vol. 280; no. 14; p. 14264
Main Authors: Valentinis, Barbara, Bianchi, Alessandro, Zhou, Dan, Cipponi, Arcadi, Catalanotti, Federica, Russo, Vincenzo, Traversari, Catia
Format: Journal Article
Language:English
Published: United States 08.04.2005
Subjects:
Anti-Bacterial Agents - pharmacology
Antigens, CD - genetics
Antigens, CD - metabolism
B7-2 Antigen
Cell Adhesion - drug effects
Cell Adhesion - physiology
Cells, Cultured
Cytokines - metabolism
Dendritic Cells - cytology
Dendritic Cells - drug effects
Dendritic Cells - immunology
Dendritic Cells - physiology
Enzyme Activation
Enzyme Inhibitors - metabolism
Extracellular Signal-Regulated MAP Kinases - metabolism
Flavonoids - metabolism
Genes, MHC Class I
Genes, MHC Class II
HLA Antigens - genetics
HLA Antigens - metabolism
Humans
I-kappa B Proteins - metabolism
Membrane Glycoproteins - genetics
Membrane Glycoproteins - metabolism
NF-kappa B - metabolism
NF-KappaB Inhibitor alpha
p38 Mitogen-Activated Protein Kinases - metabolism
Polymyxin B - pharmacology
Signal Transduction - physiology
Tosylphenylalanyl Chloromethyl Ketone - metabolism
ISSN:0021-9258
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Summary:Polymyxin B is a lipopolysaccharide binding antibiotic used to inactivate potential lipopolysaccharide contaminations when evaluating the activity of different agents on innate immune cells. We report that polymyxin B is able to induce directly in monocyte-derived human dendritic cells (DCs) several functional and molecular modifications characteristic of DCs undergoing a maturation process. DCs incubated with polymyxin B up-regulate the expression of HLA class I and II, the co-stimulatory CD86 molecule, and show an increase in the fraction of adherent cells at short time, which persist at 48 h of incubation. Adhesion to the plate was required for the polymyxin B-induced DCs maturation. A transient activation of IkappaB-alpha/NF-kappaB and ERK1/2 pathways at short time and a further ERK1/2 activation at long term were also detected. Neither up-regulation of the maturation marker CD83 nor activation of p38 nor induction of cytokines secretion was observed in DCs treated with polymyxin B. We demonstrated that inhibition of IkappaB-alpha/NF-kappaB pathway abolishes polymyxin B effects. ERK1/2 inhibition instead allowed DCs treated with polymyxin B to progress in their maturation process as revealed by the increased up-regulation of the CD83 co-stimulatory molecules, the activation of p38, and the reduced adhesion to culture plates at 48 h of incubation. Our results indicate that polymyxin B induces a partial maturation of human DCs through increased adhesion to a substrate and activation of the IkappaB-alpha/NF-kappaB pathway. The increased ERK1/2 activation observed, even though correlating with the initial phases of the maturation process, actually inhibits the occurrence of full maturation.
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ISSN:0021-9258
DOI:10.1074/jbc.M410791200