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 journalArticlepeer-review

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

ASJC Scopus subject areas

  • Biochemistry

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