10.6084/M9.FIGSHARE.21070341.V1
Gan Zhang
Gan
Zhang
Xinying Zhu
Xinying
Zhu
Fan Yang
Fan
Yang
Juan Li
Juan
Li
Xiao Leng
Xiao
Leng
Chunfen Mo
Chunfen
Mo
Limei Li
Limei
Li
Yantang Wang
Yantang
Wang
Pseudolycorine chloride ameliorates Th17 cell-mediated central nervous system autoimmunity by restraining myeloid-derived suppressor cell expansion
<p>The alkaloids of <i>Narcissus tazetta</i> L. var. <i>Chinensis</i> Roem (Amaryllidaceae) have antitumor and antiviral activities. However, the immunopharmacological effects of one of its constituents, pseudolycorine chloride (PLY), have not been reported yet.</p> <p>We evaluated the effect of PLY on myeloid-derived suppressor cells (MDSCs) expansion and differentiation into monocyte-like MDSCs (M-MDSCs) and examined whether PLY alleviates Th17 cell-mediated experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS).</p> <p><i>In vitro</i>, MDSCs were treated with PLY (0.67, 2 and 6 μM) or solcitinib (10 μM, positive control) for 48 or 96 h, and their proliferation, expansion, and differentiation into M-MDSCs were examined by flow cytometry. Myelin oligodendrocyte glycoprotein (MOG<sub>35–55</sub>) was used to induce EAE in female C57BL/6 mice, and the mice were treated with 40 mg/kg/d PLY or 1 mg/kg/d FK-506 (tacrolimus, positive control) for 21 days. Inflammatory infiltration, spinal cord demyelination, and MDSCs and Th17 cells infiltration into the spinal cord were examined using haematoxylin and eosin staining, Luxol fast blue staining, and immunofluorescence, respectively.</p> <p><i>In vitro</i>, PLY (IC50/24 h = 6.18 μM) significantly inhibited IL-6 and GM-CSF-induced MDSCs proliferation, expansion and differentiation into M-MDSCs at all concentrations used. However, these concentrations did not show cytotoxicity. In mice, PLY (40 mg/kg) treatment alleviated EAE and inhibited inflammatory infiltration, demyelination, and MDSCs and Th17 cells infiltration into the spinal cord.</p> <p>PLY may be an excellent candidate for the treatment of MS and other autoimmune diseases.</p>
Biochemistry
Cell Biology
Molecular Biology
Neuroscience
Physiology
Pharmacology
Biotechnology
Chemical Sciences not elsewhere classified
Immunology
Developmental Biology
Cancer
Plant Biology
Taylor & Francis
2022
2022-09-09
2024-03-25
Figure
22543320 Bytes
10.6084/m9.figshare.21070341
10.1080/13880209.2022.2063344
CC BY 4.0