Direct effects of polymyxin B on human dendritic cells maturation: The role of IκB-α/NF-κB and ERK1/2 pathways and adhesion

Barbara Valentinis, Alessandro Bianchi, Dan Zhou, Arcadi Cipponi, Federica Catalanotti, Vincenzo Russo, Catia Traversari

Research output: Contribution to journalArticle

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Abstract

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 IκB-α/NF-κB 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 IκB-α/NF-κB 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 IκB-α/NF-κB 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.

Original languageEnglish
Pages (from-to)14264-14271
Number of pages8
JournalJournal of Biological Chemistry
Volume280
Issue number14
DOIs
Publication statusPublished - Apr 8 2005

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Polymyxin B
MAP Kinase Signaling System
Dendritic Cells
Adhesion
Chemical activation
Up-Regulation
Lipopolysaccharides
Molecules
Monocytes
Contamination
Cytokines
Anti-Bacterial Agents
Substrates

ASJC Scopus subject areas

  • Biochemistry

Cite this

Direct effects of polymyxin B on human dendritic cells maturation : The role of IκB-α/NF-κB and ERK1/2 pathways and adhesion. / Valentinis, Barbara; Bianchi, Alessandro; Zhou, Dan; Cipponi, Arcadi; Catalanotti, Federica; Russo, Vincenzo; Traversari, Catia.

In: Journal of Biological Chemistry, Vol. 280, No. 14, 08.04.2005, p. 14264-14271.

Research output: Contribution to journalArticle

Valentinis, Barbara ; Bianchi, Alessandro ; Zhou, Dan ; Cipponi, Arcadi ; Catalanotti, Federica ; Russo, Vincenzo ; Traversari, Catia. / Direct effects of polymyxin B on human dendritic cells maturation : The role of IκB-α/NF-κB and ERK1/2 pathways and adhesion. In: Journal of Biological Chemistry. 2005 ; Vol. 280, No. 14. pp. 14264-14271.
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