Schaeffer Evelyne, Sánchez-Fernández Elena M, Gonçalves-Pereira Rita, Flacher Vincent, Lamon Delphine, Duval Monique, Fauny Jean-Daniel, Fernández José M García, Mueller Christopher G, Mellet Carmen Ortiz
In: European Journal of Medicinal Chemistry, vol. 169, pp. 111–120, 2019, ISSN: 1768-3254.
Abstract | Links | BibTeX | Tags: Activation, Acute Disease, Animals, antagonists & inhibitors, CD14, Cells, chemical synthesis, Chemistry, CO-RECEPTOR, Cultured, Dendritic cell, Dendritic Cells, Dose-Response Relationship, Drug, drug effects, drug therapy, Glycolipid, Glycolipids, Human, Humans, Iminosugar, immunopathology, IN VITRO, In vivo, Inbred C57BL, inflammation, Interleukin-6, lipopolysaccharide, Lipopolysaccharides, LPS, Male, Maturation, metabolism, Mice, MICROGLIA, Molecular Structure, mouse, pathology, Pharmacology, PRODUCTION, Receptor, signaling, Structure-Activity Relationship, Sulfone, Sulfoxide, Tail, target, Team-Mueller
@article{schaeffer_sp2-iminosugar_2019,
title = {sp2-Iminosugar glycolipids as inhibitors of lipopolysaccharide-mediated human dendritic cell activation in vitro and of acute inflammation in mice in vivo},
author = {Evelyne Schaeffer and Elena M Sánchez-Fernández and Rita Gonçalves-Pereira and Vincent Flacher and Delphine Lamon and Monique Duval and Jean-Daniel Fauny and José M García Fernández and Christopher G Mueller and Carmen Ortiz Mellet},
doi = {10.1016/j.ejmech.2019.02.078},
issn = {1768-3254},
year = {2019},
date = {2019-05-01},
journal = {European Journal of Medicinal Chemistry},
volume = {169},
pages = {111--120},
abstract = {Glycolipid mimetics consisting of a bicyclic polyhydroxypiperidine-cyclic carbamate core and a pseudoanomeric hydrophobic tail, termed sp2-iminosugar glycolipids (sp2-IGLs), target microglia during neuroinflammatory processes. Here we have synthesized and investigated new variants of sp2-IGLs for their ability to suppress the activation of human monocyte-derived dendritic cells (DCs) by lipopolysaccharide (LPS) signaling through Toll-like receptor 4. We report that the best lead was (1R)-1-dodecylsulfonyl-5N,6O-oxomethylidenenojirimycin (DSO2-ONJ), able to inhibit LPS-induced TNFα production and maturation of DCs. Immunovisualization experiments, using a mannoside glycolipid conjugate (MGC) that also suppress LPS-mediated DC activation as control, evidenced a distinct mode of action for the sp2-IGLs: unlike MGCs, DSO2-ONJ did not elicit internalization of the LPS co-receptor CD14 or induce its co-localization with the Toll-like receptor 4. In a mouse model of LPS-induced acute inflammation, DSO2-ONJ demonstrated anti-inflammatory activity by inhibiting the production of the pro-inflammatory interleukin-6. The ensemble of the data highlights sp2-IGLs as a promising new class of molecules against inflammation by interfering in Toll-like receptor intracellular signaling.},
keywords = {Activation, Acute Disease, Animals, antagonists & inhibitors, CD14, Cells, chemical synthesis, Chemistry, CO-RECEPTOR, Cultured, Dendritic cell, Dendritic Cells, Dose-Response Relationship, Drug, drug effects, drug therapy, Glycolipid, Glycolipids, Human, Humans, Iminosugar, immunopathology, IN VITRO, In vivo, Inbred C57BL, inflammation, Interleukin-6, lipopolysaccharide, Lipopolysaccharides, LPS, Male, Maturation, metabolism, Mice, MICROGLIA, Molecular Structure, mouse, pathology, Pharmacology, PRODUCTION, Receptor, signaling, Structure-Activity Relationship, Sulfone, Sulfoxide, Tail, target, Team-Mueller},
pubstate = {published},
tppubtype = {article}
}
Flacher Vincent, Neuberg Patrick, Point Floriane, Daubeuf François, Muller Quentin, Sigwalt David, Fauny Jean-Daniel, Remy Jean-Serge, Frossard Nelly, Wagner Alain, Mueller Christopher G, Schaeffer Evelyne
Mannoside Glycolipid Conjugates Display Anti-inflammatory Activity by Inhibition of Toll-like Receptor-4 Mediated Cell Activation Journal Article
In: ACS chemical biology, vol. 10, no. 12, pp. 2697–2705, 2015, ISSN: 1554-8937.
Abstract | Links | BibTeX | Tags: Activation, Animals, Anti-Inflammatory Agents, Carbohydrate Sequence, CD14, Cell Membrane, Cells, Chemistry, Cultured, cytokine, Dendritic Cells, development, disease, Glycolipids, Human, Humans, immunopathology, Inbred BALB C, inflammation, inhibition, lipid, lipopolysaccharide, Lipopolysaccharides, LPS, LUNG, Mannosides, Maturation, Membrane, Mice, monocyte, Monocytes, mouse, neutrophils, NF-kappaB, Pneumonia, Protein-Serine-Threonine Kinases, Receptor, secretion, signaling, Structure-Activity Relationship, Tail, Team-Mueller, TLR4, Toll-Like Receptor 4
@article{flacher_mannoside_2015b,
title = {Mannoside Glycolipid Conjugates Display Anti-inflammatory Activity by Inhibition of Toll-like Receptor-4 Mediated Cell Activation},
author = {Vincent Flacher and Patrick Neuberg and Floriane Point and François Daubeuf and Quentin Muller and David Sigwalt and Jean-Daniel Fauny and Jean-Serge Remy and Nelly Frossard and Alain Wagner and Christopher G Mueller and Evelyne Schaeffer},
doi = {10.1021/acschembio.5b00552},
issn = {1554-8937},
year = {2015},
date = {2015-12-01},
journal = {ACS chemical biology},
volume = {10},
number = {12},
pages = {2697--2705},
abstract = {Inhibition of excessive Toll-like receptor 4 (TLR4) signaling is a therapeutic approach pursued for many inflammatory diseases. We report that Mannoside Glycolipid Conjugates (MGCs) selectively blocked TLR4-mediated activation of human monocytes and monocyte-derived dendritic cells (DCs) by lipopolysaccharide (LPS). They potently suppressed pro-inflammatory cytokine secretion and maturation of DCs exposed to LPS, leading to impaired T cell stimulation. MGCs did not interfere with LPS and could act in a delayed manner, hours after LPS stimulation. Their inhibitory action required both the sugar heads and the lipid chain, although the nature of the sugar and the structure of the lipid tail could be modified. They blocked early signaling events at the cell membrane, enhanced internalization of CD14 receptors, and prevented colocalization of CD14 and TLR4, thereby abolishing NF-κB nuclear translocation. When the best lead conjugate was tested in a mouse model of LPS-induced acute lung inflammation, it displayed an anti-inflammatory action by suppressing the recruitment of neutrophils. Thus, MGCs could serve as promising leads for the development of selective TLR4 antagonistic agents for inflammatory diseases.},
keywords = {Activation, Animals, Anti-Inflammatory Agents, Carbohydrate Sequence, CD14, Cell Membrane, Cells, Chemistry, Cultured, cytokine, Dendritic Cells, development, disease, Glycolipids, Human, Humans, immunopathology, Inbred BALB C, inflammation, inhibition, lipid, lipopolysaccharide, Lipopolysaccharides, LPS, LUNG, Mannosides, Maturation, Membrane, Mice, monocyte, Monocytes, mouse, neutrophils, NF-kappaB, Pneumonia, Protein-Serine-Threonine Kinases, Receptor, secretion, signaling, Structure-Activity Relationship, Tail, Team-Mueller, TLR4, Toll-Like Receptor 4},
pubstate = {published},
tppubtype = {article}
}
Bechetoille N, Vachon H, Gaydon A, Boher A, Fontaine T, Schaeffer E, Decossas M, Andre-Frei V, Mueller C G
A new organotypic model containing dermal-type macrophages Journal Article
In: Experimental Dermatology, vol. 20, no. 1600-0625 (Electronic), pp. 1035–1037, 2011.
Abstract | BibTeX | Tags: CELL CULTURE, Chemistry, Culture, cytokine, Dendritic Cells, DERMATOLOGY, Fibroblast, Fibroblasts, HLA-DR, Human, IL-10, IL10, Immunology, Latex, Letter, lipopolysaccharide, LPS, Macrophage, Macrophages, monocyte, Monocytes, Skin, Team-Mueller
@article{bechetoille_new_2011,
title = {A new organotypic model containing dermal-type macrophages},
author = {N Bechetoille and H Vachon and A Gaydon and A Boher and T Fontaine and E Schaeffer and M Decossas and V Andre-Frei and C G Mueller},
year = {2011},
date = {2011-01-01},
journal = {Experimental Dermatology},
volume = {20},
number = {1600-0625 (Electronic)},
pages = {1035--1037},
abstract = {Human skin equivalents (SEs) are popular three-dimensional (D) cell culture systems in fundamental and applied dermatology. They have been made to contain dendritic cells, but so far no study on the incorporation of potentially anti-inflammatory dermal macrophages has been performed. Here, we show that monocyte-derived dermal-type macrophages can be introduced into a rigid scaffold with dermal fibroblasts. They maintain their cell surface markers CD163, DC-SIGN/CD209 and HLA-DR, which discriminate them from monocytes and dendritic cells. They retain the ability to produce the anti-inflammatory cytokine IL-10 in response to lipopolysaccharide (LPS) and to phagocytose latex beads. We thus demonstrate the feasibility of creating macrophage-fibroblast 3D cultures as a first step towards generating SEs with dermal macrophages},
keywords = {CELL CULTURE, Chemistry, Culture, cytokine, Dendritic Cells, DERMATOLOGY, Fibroblast, Fibroblasts, HLA-DR, Human, IL-10, IL10, Immunology, Latex, Letter, lipopolysaccharide, LPS, Macrophage, Macrophages, monocyte, Monocytes, Skin, Team-Mueller},
pubstate = {published},
tppubtype = {article}
}
Kwan W H, Boix C, Gougelet N, Fridman W H, Mueller C G
LPS induces rapid IL-10 release by M-CSF-conditioned tolerogenic dendritic cell precursors Journal Article
In: Journal of Leukocyte Biology, vol. 82, no. 0741-5400 (Print), pp. 133–141, 2007.
Abstract | BibTeX | Tags: Activation, APC, Cell Differentiation, COLONY-STIMULATING FACTOR, cytokine, Cytokines, cytology, Dendritic Cells, Differentiation, GM-CSF, Human, Humans, IL-10, IL10, IMMATURE, immune response, Immune Tolerance, Immunity, Immunology, inflammation, interleukin 10, Interleukin-10, lipopolysaccharide, Lipopolysaccharides, LPS, Macrophage, Macrophage Colony-Stimulating Factor, Maturation, metabolism, MODULATION, monocyte, Monocytes, MYCOBACTERIA, Mycobacterium, Myeloid Cells, Pharmacology, precursor, PRODUCTION, Protein, Receptor, Secondary, T CELL ACTIVATION, Team-Mueller
@article{kwan_lps_2007,
title = {LPS induces rapid IL-10 release by M-CSF-conditioned tolerogenic dendritic cell precursors},
author = {W H Kwan and C Boix and N Gougelet and W H Fridman and C G Mueller},
year = {2007},
date = {2007-07-01},
journal = {Journal of Leukocyte Biology},
volume = {82},
number = {0741-5400 (Print)},
pages = {133--141},
abstract = {Dendritic cells (DC) obtained by culturing myeloid precursors in GM-CSF undergo maturation and induce an efficient T cell response when stimulated with microbial products. DC precursors themselves also recognize microbial products, and it remains unclear how these stimulated DC precursors modulate the immune response. We show here that M-CSF-conditioned human DC precursors responded to LPS, Mycobacteria bovis, and inflammatory cytokines by a rapid and robust production of IL-10, largely superior to that observed with immature DC or monocytes. The endogenous IL-10 restrained the DC precursors from converting into professional APC, as blocking the IL-10 receptor in the presence of LPS resulted in the formation of efficient T cell stimulators. LPS stimulation concomitant with DC differentiation gave rise to immature DC, which were tolerant to a secondary LPS exposure. Furthermore, the LPS-activated DC precursors reduced bystander DC maturation and anti-CD3/CD28-triggered T cell activation. These data suggest that when exposed to inflammatory or microbial signals, M-CSF-conditioned DC precursors can participate in the modulation of inflammation and immune response by rapid release of IL-10},
keywords = {Activation, APC, Cell Differentiation, COLONY-STIMULATING FACTOR, cytokine, Cytokines, cytology, Dendritic Cells, Differentiation, GM-CSF, Human, Humans, IL-10, IL10, IMMATURE, immune response, Immune Tolerance, Immunity, Immunology, inflammation, interleukin 10, Interleukin-10, lipopolysaccharide, Lipopolysaccharides, LPS, Macrophage, Macrophage Colony-Stimulating Factor, Maturation, metabolism, MODULATION, monocyte, Monocytes, MYCOBACTERIA, Mycobacterium, Myeloid Cells, Pharmacology, precursor, PRODUCTION, Protein, Receptor, Secondary, T CELL ACTIVATION, Team-Mueller},
pubstate = {published},
tppubtype = {article}
}
Cremer I, Dieu-Nosjean M C, Mar�chal S, Dezutter-Dambuyant C, Goddard S, Adams D, Winter N, Menetrier-Caux C, Saut�s-Fridman C, Fridman W H, Mueller C G F
Long-lived immature dendritic cells mediated by TRANCE-RANK interaction Journal Article
In: Blood, vol. 100, no. 10, pp. 3646–3655, 2002.
Abstract | BibTeX | Tags: Activation, Antigen, CD40, CD40 Ligand, CHEMOTAXIS, Cytokines, Dendritic Cells, Epidermis, Expression, Homeostasis, Human, IMMATURE, l, ligand, lipopolysaccharide, Longevity, LPS, LYMPH, LYMPH NODE, Lymph Nodes, M-CSF, Macrophage, Macrophages, Maturation, naive, Necrosis, NF-kappaB, PROGENITOR CELLS, rank, Receptor, survival, T CELL ACTIVATION, T CELLS, Team-Mueller, TRANCE, tumor, viability
@article{cremer_long-lived_2002,
title = {Long-lived immature dendritic cells mediated by TRANCE-RANK interaction},
author = {I Cremer and M C Dieu-Nosjean and S Mar�chal and C Dezutter-Dambuyant and S Goddard and D Adams and N Winter and C Menetrier-Caux and C Saut�s-Fridman and W H Fridman and C G F Mueller},
year = {2002},
date = {2002-01-01},
journal = {Blood},
volume = {100},
number = {10},
pages = {3646--3655},
abstract = {Immature dendritic cells (DCs) reside in Interstitial tissues (Int-DC) or in the epidermis, where they capture antigen and, thereafter, mature and migrate to draining lymph nodes (LNs), where they present processed antigen to T cells. We have Identified Int-DCs that express both TRANCE (tumor necrosis factor-related activation-induced cytokine) and RANK (receptor activator of NF-kappaB) and have generated these cells from CD34(+) human progenitor cells using macrophage colony-stimulating factor (M-CSF). These CD34(+)-derived Int-DCs, which are related to macrophages, are long-lived, but addition of soluble RANK leads to significant reduction of cell viability and BcI-2 expression. This suggests that constitutive TRANCE-RANK interaction is responsible for CD34(+)-derived Int-DC longevity. Conversely, CD1a(+) DCs express only RANK and are short-lived. However, they can be rescued from cell death either by recombinant soluble TRANCE or by CD34(+)-derived Int-DCs. CD34(+)-derived Int-DCs mature in response to lipopolysaccharide (LPS) plus CD40 ligand (L) and become capable of CCL21/CCL19-mediated chemotaxis and naive T-cell activation. Upon maturation, they lose TRANCE, making them, like CD1a(+) DCs, dependent on exogenous TRANCE for survival. These findings provide evidence that TRANCE and RANK play important roles in the homeostasis of DCs. (C) 2002 by The American Society of Hematology},
keywords = {Activation, Antigen, CD40, CD40 Ligand, CHEMOTAXIS, Cytokines, Dendritic Cells, Epidermis, Expression, Homeostasis, Human, IMMATURE, l, ligand, lipopolysaccharide, Longevity, LPS, LYMPH, LYMPH NODE, Lymph Nodes, M-CSF, Macrophage, Macrophages, Maturation, naive, Necrosis, NF-kappaB, PROGENITOR CELLS, rank, Receptor, survival, T CELL ACTIVATION, T CELLS, Team-Mueller, TRANCE, tumor, viability},
pubstate = {published},
tppubtype = {article}
}