Laquinimod dampens IL-1β signaling and Th17-polarizing capacity of monocytes in patients with MS
Objective To assess the impact of laquinimod treatment on monocytes and to investigate the underlying immunomodulatory mechanisms in MS. - Methods In this cross-sectional study, we performed in vivo and in vitro analyses of cluster of differentiation (CD14+) monocytes isolated from healthy donors (n...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
2021
|
| In: |
Neurology: Neuroimmunology & Neuroinflammation ; official journal of the American Academy of Neurology
Year: 2020, Volume: 8, Issue: 1, Pages: 1-10 |
| ISSN: | 2332-7812 |
| DOI: | 10.1212/NXI.0000000000000908 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1212/NXI.0000000000000908 Verlag, lizenzpflichtig, Volltext: https://nn.neurology.org/content/8/1/e908 
|
| Author Notes: | Sinah Engel, MD, Valérie Jolivel, PhD, Stefan H.-P. Kraus, PhD, Morad Zayoud, MD, Karolina Rosenfeld, Hayrettin Tumani, MD, Roberto Furlan, MD, PhD, Florian C. Kurschus, PhD, Ari Waisman, PhD, and Felix Luessi, MD |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1750097273 | ||
| 003 | DE-627 | ||
| 005 | 20220819123036.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 210302r20212020xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1212/NXI.0000000000000908 |2 doi | |
| 035 | |a (DE-627)1750097273 | ||
| 035 | |a (DE-599)KXP1750097273 | ||
| 035 | |a (OCoLC)1341396579 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Engel, Sinah |d 1990- |e VerfasserIn |0 (DE-588)1215642806 |0 (DE-627)172675121X |4 aut | |
| 245 | 1 | 0 | |a Laquinimod dampens IL-1β signaling and Th17-polarizing capacity of monocytes in patients with MS |c Sinah Engel, MD, Valérie Jolivel, PhD, Stefan H.-P. Kraus, PhD, Morad Zayoud, MD, Karolina Rosenfeld, Hayrettin Tumani, MD, Roberto Furlan, MD, PhD, Florian C. Kurschus, PhD, Ari Waisman, PhD, and Felix Luessi, MD |
| 246 | 3 | 3 | |a Laquinimod dampens IL-one beta signaling and Th seventeen-polarizing capacity of monocytes in patients with MS |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a First published November 17, 2020 | ||
| 500 | |a Gesehen am 02.03.2021 | ||
| 520 | |a Objective To assess the impact of laquinimod treatment on monocytes and to investigate the underlying immunomodulatory mechanisms in MS. - Methods In this cross-sectional study, we performed in vivo and in vitro analyses of cluster of differentiation (CD14+) monocytes isolated from healthy donors (n = 15), untreated (n = 13), and laquinimod-treated patients with MS (n = 14). Their frequency and the expression of surface activation markers were assessed by flow cytometry and the viability by calcein staining. Cytokine concentrations in the supernatants of lipopolysaccharide (LPS)-stimulated monocytes were determined by flow cytometry. The messenger ribonucleic acid (mRNA) expression level of genes involved in cytokine expression was measured by quantitative PCR. The LPS-mediated nuclear factor kappa-light-chain-enhancer of activated B-cell (NF-κB) activation was determined by the quantification of the phosphorylation level of the p65 subunit. Laquinimod-treated monocytes were cocultured with CD4+ T cells, and the resulting cytokine production was analyzed by flow cytometry after intracellular cytokine staining. The interleukin (IL)-17A concentration of the supernatant was assessed by ELISA. - Results Laquinimod did not alter the frequency or viability of circulating monocytes, but led to an upregulation of CD86 expression. LPS-stimulated monocytes of laquinimod-treated patients with MS secreted less IL-1β following a downregulation of IL-1β gene expression. Phosphorylation levels of the NF-κB p65 subunit were reduced after laquinimod treatment, indicating a laquinimod-associated inhibition of the NF-κB pathway. T cells primed with laquinimod-treated monocytes differentiated significantly less into IL-17A-producing T helper (Th)-17 cells. - Conclusions Our findings suggest that inhibited NF-κB signaling and downregulation of IL-1β expression in monocytes contributes to the immunomodulatory effects of laquinimod and that the impairment of Th17 polarization might mediate its disease-modifying activity in MS. | ||
| 534 | |c 2020 | ||
| 700 | 1 | |a Jolivel, Valérie |e VerfasserIn |4 aut | |
| 700 | 1 | |a Kraus, Stefan H.-P. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Zayoud, Morad |e VerfasserIn |4 aut | |
| 700 | 1 | |a Rosenfeld, Karolina |e VerfasserIn |4 aut | |
| 700 | 1 | |a Tumani, Hayrettin |e VerfasserIn |4 aut | |
| 700 | 1 | |a Furlan, Roberto |e VerfasserIn |4 aut | |
| 700 | 1 | |a Kurschus, Florian |d 1969- |e VerfasserIn |0 (DE-588)122999916 |0 (DE-627)706122887 |0 (DE-576)29351464X |4 aut | |
| 700 | 1 | |a Waisman, Ari |e VerfasserIn |4 aut | |
| 700 | 1 | |a Luessi, Felix |e VerfasserIn |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Neurology: Neuroimmunology & Neuroinflammation ; official journal of the American Academy of Neurology |d Philadelphia, Pa. : Wolters Kluwer, 2014 |g 8(2021,1) Artikel-Nummer e908, 10 Seiten |h Online-Ressource |w (DE-627)784191956 |w (DE-600)2767740-0 |w (DE-576)404866883 |x 2332-7812 |7 nnas |a Laquinimod dampens IL-1β signaling and Th17-polarizing capacity of monocytes in patients with MS |
| 773 | 1 | 8 | |g volume:8 |g year:2021 |g number:1 |g elocationid:e908 |g pages:1-10 |a Laquinimod dampens IL-1β signaling and Th17-polarizing capacity of monocytes in patients with MS |
| 856 | 4 | 0 | |u https://doi.org/10.1212/NXI.0000000000000908 |x Verlag |x Resolving-System |z lizenzpflichtig |3 Volltext |
| 856 | 4 | 0 | |u https://nn.neurology.org/content/8/1/e908 |x Verlag |z lizenzpflichtig |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20210302 | ||
| 993 | |a Article | ||
| 994 | |a 2021 | ||
| 998 | |g 122999916 |a Kurschus, Florian |m 122999916:Kurschus, Florian |d 910000 |d 911300 |e 910000PK122999916 |e 911300PK122999916 |k 0/910000/ |k 1/910000/911300/ |p 8 | ||
| 999 | |a KXP-PPN1750097273 |e 3879858055 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"relHost":[{"title":[{"title":"Neurology: Neuroimmunology & Neuroinflammation ; official journal of the American Academy of Neurology","title_sort":"Neurology: Neuroimmunology & Neuroinflammation ; official journal of the American Academy of Neurology"}],"language":["eng"],"disp":"Laquinimod dampens IL-1β signaling and Th17-polarizing capacity of monocytes in patients with MSNeurology: Neuroimmunology & Neuroinflammation ; official journal of the American Academy of Neurology","part":{"issue":"1","pages":"1-10","year":"2021","text":"8(2021,1) Artikel-Nummer e908, 10 Seiten","volume":"8"},"physDesc":[{"extent":"Online-Ressource"}],"note":["Gesehen am 28.04.14"],"type":{"bibl":"periodical","media":"Online-Ressource"},"origin":[{"publisher":"Wolters Kluwer ; Lippincott Williams & Wilkins","dateIssuedDisp":"2014-","publisherPlace":"Philadelphia, Pa. ; Philadelphia, Pa.","dateIssuedKey":"2014"}],"pubHistory":["1.2014 -"],"recId":"784191956","id":{"issn":["2332-7812"],"eki":["784191956"],"zdb":["2767740-0"]}}],"person":[{"role":"aut","family":"Engel","display":"Engel, Sinah","roleDisplay":"VerfasserIn","given":"Sinah"},{"family":"Jolivel","display":"Jolivel, Valérie","roleDisplay":"VerfasserIn","given":"Valérie","role":"aut"},{"role":"aut","family":"Kraus","roleDisplay":"VerfasserIn","display":"Kraus, Stefan H.-P.","given":"Stefan H.-P."},{"role":"aut","display":"Zayoud, Morad","roleDisplay":"VerfasserIn","given":"Morad","family":"Zayoud"},{"roleDisplay":"VerfasserIn","display":"Rosenfeld, Karolina","given":"Karolina","family":"Rosenfeld","role":"aut"},{"family":"Tumani","display":"Tumani, Hayrettin","roleDisplay":"VerfasserIn","given":"Hayrettin","role":"aut"},{"role":"aut","family":"Furlan","display":"Furlan, Roberto","roleDisplay":"VerfasserIn","given":"Roberto"},{"family":"Kurschus","roleDisplay":"VerfasserIn","display":"Kurschus, Florian","given":"Florian","role":"aut"},{"role":"aut","family":"Waisman","roleDisplay":"VerfasserIn","display":"Waisman, Ari","given":"Ari"},{"role":"aut","family":"Luessi","given":"Felix","roleDisplay":"VerfasserIn","display":"Luessi, Felix"}],"note":["First published November 17, 2020","Gesehen am 02.03.2021"],"type":{"media":"Online-Ressource","bibl":"article-journal"},"titleAlt":[{"title":"Laquinimod dampens IL-one beta signaling and Th seventeen-polarizing capacity of monocytes in patients with MS"}],"title":[{"title":"Laquinimod dampens IL-1β signaling and Th17-polarizing capacity of monocytes in patients with MS","title_sort":"Laquinimod dampens IL-1β signaling and Th17-polarizing capacity of monocytes in patients with MS"}],"language":["eng"],"recId":"1750097273","id":{"eki":["1750097273"],"doi":["10.1212/NXI.0000000000000908"]},"name":{"displayForm":["Sinah Engel, MD, Valérie Jolivel, PhD, Stefan H.-P. Kraus, PhD, Morad Zayoud, MD, Karolina Rosenfeld, Hayrettin Tumani, MD, Roberto Furlan, MD, PhD, Florian C. Kurschus, PhD, Ari Waisman, PhD, and Felix Luessi, MD"]},"origin":[{"dateIssuedKey":"2021","dateIssuedDisp":"2021"}]} | ||
| SRT | |a ENGELSINAHLAQUINIMOD2021 | ||