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LPS response and endotoxin tolerance in Flt-3L-induced bone marrow-derived dendritic cells

Patenaude, Julie; D'Elia, Michele; Côté-Maurais, Guillaume et Bernier, Jacques ORCID logoORCID: https://orcid.org/0000-0002-0594-5922 (2011). LPS response and endotoxin tolerance in Flt-3L-induced bone marrow-derived dendritic cells Cellular Immunology , vol. 271 , nº 1. pp. 184-191. DOI: 10.1016/j.cellimm.2011.06.020.

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Résumé


Fms-like tyrosine kinase-3 ligand (Flt-3L) stimulates the differentiation of bone marrow cells into dendritic cells (DCs) and was used as an adjuvant therapy in the experimental model of burn wound sepsis. In this study, we describe the phenotypical characteristics of an Flt-3L-dependent DC culture (FLDC) system following LPS stimulation, which induces an inflammatory response, and after a second LPS stimulation, which induces tolerance. Priming of FLDCs with LPS via TLR4 has been shown to induce the activation of all three mitogen-activated protein kinase (MAPK) families and enhance NF-kappaB complex translocation into the nucleus. Stimulated FLDCs express all maturation markers and exhibit an increase in IL-12p40 production and to a lesser extent, IL-10 production. In contrast, LPS stimulation of tolerized FLDCs was not associated with TLR4 up-regulation and led to MAPK inhibition. The decrease in p38 and JNK activation was correlated with an impairment of IL-12p40 production. Endotoxin tolerance in FLDCs was associated with enhanced ERK1/2 activation, an increase in MKP-1 phosphatase expression, a decrease in NF-kappaB translocation to the nucleus and an increase in IL-10 production. Overall, DCs generated from bone marrow with Flt-3 ligand have similar characteristics to DC subtypes found in the steady state in vivo, which can acquire endotoxin tolerance in some circumstances.

Type de document: Article
Mots-clés libres: Flt-3L; Bone marrow; Dendritic cells; Endotoxin; Tolerance; MAP kinase; MKP-1 IL-10 IL-12
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 29 mars 2024 21:18
Dernière modification: 29 mars 2024 21:18
URI: https://espace.inrs.ca/id/eprint/15036

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