Panax notoginseng saponins (PNS) attenuate Th17 cell differentiation in CIA mice via inhibition of nuclear PKM2-mediated STAT3 phosphorylation
CONTEXT: Rheumatoid arthritis (RA) is an autoimmune disease with aberrant Th17 cell differentiation. Panax notoginseng (Burk.) F. H. Chen (Araliaceae) saponins (PNS) have an anti-inflammatory effect and can suppress Th17 cell differentiation.
OBJECTIVE: To investigate mechanisms of PNS on Th17 cell differentiation in RA, and the role of pyruvate kinase M2 (PKM2).
MATERIALS AND METHODS: Naive CD4+T cells were treated with IL-6, IL-23 and TGF-β to induce Th17 cell differentiation. Apart from the Control group, other cells were treated with PNS (5, 10, 20 μg/mL). After the treatment, Th17 cell differentiation, PKM2 expression, and STAT3 phosphorylation were measured via flow cytometry, western blots, or immunofluorescence. PKM2-specific allosteric activator (Tepp-46, 50, 100, 150 μM) and inhibitor (SAICAR, 2, 4, 8 μM) were used to verify the mechanisms. A CIA mouse model was established and divided into control, model, and PNS (100 mg/kg) groups to assess an anti-arthritis effect, Th17 cell differentiation, and PKM2/STAT3 expression.
RESULTS: PKM2 expression, dimerization, and nuclear accumulation were upregulated upon Th17 cell differentiation. PNS inhibited the Th17 cells, RORγt expression, IL-17A levels, PKM2 dimerization, and nuclear accumulation and Y705-STAT3 phosphorylation in Th17 cells. Using Tepp-46 (100 μM) and SAICAR (4 μM), we demonstrated that PNS (10 μg/mL) inhibited STAT3 phosphorylation and Th17 cell differentiation by suppressing nuclear PKM2 accumulation. In CIA mice, PNS attenuated CIA symptoms, reduced the number of splenic Th17 cells and nuclear PKM2/STAT3 signaling.
DISCUSSION AND CONCLUSIONS: PNS inhibited Th17 cell differentiation through the inhibition of nuclear PKM2-mediated STAT3 phosphorylation. PNS may be useful for treating RA.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:61 |
|---|---|
| Enthalten in: |
Pharmaceutical biology - 61(2023), 1 vom: 13. Dez., Seite 459-472 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Shen, Mei-Yu [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Autoimmune disease |
|---|
| Anmerkungen: |
Date Completed 17.02.2023 Date Revised 20.02.2023 published: Print Citation Status MEDLINE |
|---|
| doi: |
10.1080/13880209.2023.2173248 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM353012564 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM353012564 | ||
| 003 | DE-627 | ||
| 005 | 20231226055027.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1080/13880209.2023.2173248 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1176.xml |
| 035 | |a (DE-627)NLM353012564 | ||
| 035 | |a (NLM)36794740 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Shen, Mei-Yu |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Panax notoginseng saponins (PNS) attenuate Th17 cell differentiation in CIA mice via inhibition of nuclear PKM2-mediated STAT3 phosphorylation |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 17.02.2023 | ||
| 500 | |a Date Revised 20.02.2023 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a CONTEXT: Rheumatoid arthritis (RA) is an autoimmune disease with aberrant Th17 cell differentiation. Panax notoginseng (Burk.) F. H. Chen (Araliaceae) saponins (PNS) have an anti-inflammatory effect and can suppress Th17 cell differentiation | ||
| 520 | |a OBJECTIVE: To investigate mechanisms of PNS on Th17 cell differentiation in RA, and the role of pyruvate kinase M2 (PKM2) | ||
| 520 | |a MATERIALS AND METHODS: Naive CD4+T cells were treated with IL-6, IL-23 and TGF-β to induce Th17 cell differentiation. Apart from the Control group, other cells were treated with PNS (5, 10, 20 μg/mL). After the treatment, Th17 cell differentiation, PKM2 expression, and STAT3 phosphorylation were measured via flow cytometry, western blots, or immunofluorescence. PKM2-specific allosteric activator (Tepp-46, 50, 100, 150 μM) and inhibitor (SAICAR, 2, 4, 8 μM) were used to verify the mechanisms. A CIA mouse model was established and divided into control, model, and PNS (100 mg/kg) groups to assess an anti-arthritis effect, Th17 cell differentiation, and PKM2/STAT3 expression | ||
| 520 | |a RESULTS: PKM2 expression, dimerization, and nuclear accumulation were upregulated upon Th17 cell differentiation. PNS inhibited the Th17 cells, RORγt expression, IL-17A levels, PKM2 dimerization, and nuclear accumulation and Y705-STAT3 phosphorylation in Th17 cells. Using Tepp-46 (100 μM) and SAICAR (4 μM), we demonstrated that PNS (10 μg/mL) inhibited STAT3 phosphorylation and Th17 cell differentiation by suppressing nuclear PKM2 accumulation. In CIA mice, PNS attenuated CIA symptoms, reduced the number of splenic Th17 cells and nuclear PKM2/STAT3 signaling | ||
| 520 | |a DISCUSSION AND CONCLUSIONS: PNS inhibited Th17 cell differentiation through the inhibition of nuclear PKM2-mediated STAT3 phosphorylation. PNS may be useful for treating RA | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a CD4+T cells | |
| 650 | 4 | |a Immunometabolism | |
| 650 | 4 | |a Panax notoginseng saponins | |
| 650 | 4 | |a autoimmune disease | |
| 650 | 4 | |a glycolysis | |
| 650 | 7 | |a Saponins |2 NLM | |
| 700 | 1 | |a Di, Yu-Xi |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xiang |e verfasserin |4 aut | |
| 700 | 1 | |a Tian, Feng-Xiang |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Ming-Fei |e verfasserin |4 aut | |
| 700 | 1 | |a Qian, Fei-Ya |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Bao-Ping |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Xue-Ping |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Ling-Ling |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Pharmaceutical biology |d 1997 |g 61(2023), 1 vom: 13. Dez., Seite 459-472 |w (DE-627)NLM097504416 |x 1744-5116 |7 nnns |
| 773 | 1 | 8 | |g volume:61 |g year:2023 |g number:1 |g day:13 |g month:12 |g pages:459-472 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1080/13880209.2023.2173248 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 61 |j 2023 |e 1 |b 13 |c 12 |h 459-472 | ||