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Imperatorin Inhibits Proliferation, Migration, and Inflammation via Blocking the NF-κB and MAPK Pathways in Rheumatoid Fibroblast-like Synoviocytes

[Image: see text] Rheumatoid arthritis (RA) is a chronic joint inflammatory disease associated with the aberrant activation of fibroblast-like synoviocytes (FLSs). Searching for natural compounds that may suppress the activation of FLSs has become a complementary approach for RA treatment. Here, we...

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Autores principales: Lin, Wei, Chen, Gang, Mao, Yuhang, Ma, Xuemei, Zhou, Junnan, Yu, Xiaolu, Wang, Chaoliang, Liu, Mei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2022
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9434770/
https://www.ncbi.nlm.nih.gov/pubmed/36061691
http://dx.doi.org/10.1021/acsomega.2c02766
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author Lin, Wei
Chen, Gang
Mao, Yuhang
Ma, Xuemei
Zhou, Junnan
Yu, Xiaolu
Wang, Chaoliang
Liu, Mei
author_facet Lin, Wei
Chen, Gang
Mao, Yuhang
Ma, Xuemei
Zhou, Junnan
Yu, Xiaolu
Wang, Chaoliang
Liu, Mei
author_sort Lin, Wei
collection PubMed
description [Image: see text] Rheumatoid arthritis (RA) is a chronic joint inflammatory disease associated with the aberrant activation of fibroblast-like synoviocytes (FLSs). Searching for natural compounds that may suppress the activation of FLSs has become a complementary approach for RA treatment. Here, we investigated the effects and mechanisms of imperatorin (IPT) on proliferation, migration, and inflammation in primary cultured arthritic FLSs. We found that IPT significantly suppressed TNFα-induced proliferation and migration of arthritic FLSs, but showed little effect on survival and apoptosis. In addition, IPT treatment significantly reduced the TNFα-induced expression of pro-inflammatory cytokines (IL-1β, TNFα, IL-6, and IL-8) in arthritic FLSs. Further mechanism studies suggested that IPT inhibited the activations of p38 and extracellular signal-regulated kinase (ERK). Also, IPT blocked the nuclear factor of κB (NF-κB) activation by suppressing the phosphorylation and degradation of IκBα, thereby preventing the translocation of p65. Collectively, our results demonstrated that IPT could inhibit the over-activated phenotypes of arthritic FLSs via the mitogen-activated protein kinase (MAPK) (p38 and ERK) and NF-κB pathways leading to the down-regulation of pro-inflammatory cytokines, which might be beneficial to the anti-proliferative and anti-migratory activities of FLS cells. These findings suggest that IPT has the potential to be developed as a novel agent for RA treatment.
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spelling pubmed-94347702022-09-02 Imperatorin Inhibits Proliferation, Migration, and Inflammation via Blocking the NF-κB and MAPK Pathways in Rheumatoid Fibroblast-like Synoviocytes Lin, Wei Chen, Gang Mao, Yuhang Ma, Xuemei Zhou, Junnan Yu, Xiaolu Wang, Chaoliang Liu, Mei ACS Omega [Image: see text] Rheumatoid arthritis (RA) is a chronic joint inflammatory disease associated with the aberrant activation of fibroblast-like synoviocytes (FLSs). Searching for natural compounds that may suppress the activation of FLSs has become a complementary approach for RA treatment. Here, we investigated the effects and mechanisms of imperatorin (IPT) on proliferation, migration, and inflammation in primary cultured arthritic FLSs. We found that IPT significantly suppressed TNFα-induced proliferation and migration of arthritic FLSs, but showed little effect on survival and apoptosis. In addition, IPT treatment significantly reduced the TNFα-induced expression of pro-inflammatory cytokines (IL-1β, TNFα, IL-6, and IL-8) in arthritic FLSs. Further mechanism studies suggested that IPT inhibited the activations of p38 and extracellular signal-regulated kinase (ERK). Also, IPT blocked the nuclear factor of κB (NF-κB) activation by suppressing the phosphorylation and degradation of IκBα, thereby preventing the translocation of p65. Collectively, our results demonstrated that IPT could inhibit the over-activated phenotypes of arthritic FLSs via the mitogen-activated protein kinase (MAPK) (p38 and ERK) and NF-κB pathways leading to the down-regulation of pro-inflammatory cytokines, which might be beneficial to the anti-proliferative and anti-migratory activities of FLS cells. These findings suggest that IPT has the potential to be developed as a novel agent for RA treatment. American Chemical Society 2022-08-16 /pmc/articles/PMC9434770/ /pubmed/36061691 http://dx.doi.org/10.1021/acsomega.2c02766 Text en © 2022 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by-nc-nd/4.0/Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Lin, Wei
Chen, Gang
Mao, Yuhang
Ma, Xuemei
Zhou, Junnan
Yu, Xiaolu
Wang, Chaoliang
Liu, Mei
Imperatorin Inhibits Proliferation, Migration, and Inflammation via Blocking the NF-κB and MAPK Pathways in Rheumatoid Fibroblast-like Synoviocytes
title Imperatorin Inhibits Proliferation, Migration, and Inflammation via Blocking the NF-κB and MAPK Pathways in Rheumatoid Fibroblast-like Synoviocytes
title_full Imperatorin Inhibits Proliferation, Migration, and Inflammation via Blocking the NF-κB and MAPK Pathways in Rheumatoid Fibroblast-like Synoviocytes
title_fullStr Imperatorin Inhibits Proliferation, Migration, and Inflammation via Blocking the NF-κB and MAPK Pathways in Rheumatoid Fibroblast-like Synoviocytes
title_full_unstemmed Imperatorin Inhibits Proliferation, Migration, and Inflammation via Blocking the NF-κB and MAPK Pathways in Rheumatoid Fibroblast-like Synoviocytes
title_short Imperatorin Inhibits Proliferation, Migration, and Inflammation via Blocking the NF-κB and MAPK Pathways in Rheumatoid Fibroblast-like Synoviocytes
title_sort imperatorin inhibits proliferation, migration, and inflammation via blocking the nf-κb and mapk pathways in rheumatoid fibroblast-like synoviocytes
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9434770/
https://www.ncbi.nlm.nih.gov/pubmed/36061691
http://dx.doi.org/10.1021/acsomega.2c02766
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