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Roflumilast Reduced the IL-18-Induced Inflammatory Response in Fibroblast-Like Synoviocytes (FLS)
[Image: see text] Pro-inflammatory cytokines, such as the IL-18-induced inflammatory response and associated damage in fibroblast-like synoviocytes (FLS), play an important role in the pathogenesis of rheumatoid arthritis (RA). Roflumilast, an inhibitor of phosphodiesterase-4 (PDE-4), has been licen...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841938/ https://www.ncbi.nlm.nih.gov/pubmed/33521454 http://dx.doi.org/10.1021/acsomega.0c05281 |
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author | Zhong, Bing Guo, Shuanghong Yang, Zhongai Han, Li Du, Junsheng Chen, Jin Dun, Xianli Wang, Guangyong |
author_facet | Zhong, Bing Guo, Shuanghong Yang, Zhongai Han, Li Du, Junsheng Chen, Jin Dun, Xianli Wang, Guangyong |
author_sort | Zhong, Bing |
collection | PubMed |
description | [Image: see text] Pro-inflammatory cytokines, such as the IL-18-induced inflammatory response and associated damage in fibroblast-like synoviocytes (FLS), play an important role in the pathogenesis of rheumatoid arthritis (RA). Roflumilast, an inhibitor of phosphodiesterase-4 (PDE-4), has been licensed for the treatment of chronic obstructive pulmonary disease (COPD). However, it is unknown whether roflumilast possesses a protective effect against the IL-18-induced inflammatory response in FLS. We found that roflumilast attenuated IL-18-induced oxidative stress by reducing the production of reactive oxygen species and malondialdehyde (MDA) in MH7A fibroblast-like synoviocytes (FLS). Additionally, roflumilast prevented IL-18-induced expressions and secretions of pro-inflammatory cytokines such as IL-6, IL-8, and TNF-α. Importantly, we found that roflumilast inhibited IL-18-induced expressions of chemokines such as CCL5, CXCL9, and CXCL10. Further, roflumilast inhibited the expression of extracellular matrix degradative enzymes, such as matrix metalloproteinase-3 (MMP-3) and MMP-13. Mechanistically, we found that roflumilast suppressed the activation of the transcriptional factor AP-1 and NF-κB. Our results suggest that roflumilast might be a potential therapeutic agent for the treatment of RA. |
format | Online Article Text |
id | pubmed-7841938 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-78419382021-01-29 Roflumilast Reduced the IL-18-Induced Inflammatory Response in Fibroblast-Like Synoviocytes (FLS) Zhong, Bing Guo, Shuanghong Yang, Zhongai Han, Li Du, Junsheng Chen, Jin Dun, Xianli Wang, Guangyong ACS Omega [Image: see text] Pro-inflammatory cytokines, such as the IL-18-induced inflammatory response and associated damage in fibroblast-like synoviocytes (FLS), play an important role in the pathogenesis of rheumatoid arthritis (RA). Roflumilast, an inhibitor of phosphodiesterase-4 (PDE-4), has been licensed for the treatment of chronic obstructive pulmonary disease (COPD). However, it is unknown whether roflumilast possesses a protective effect against the IL-18-induced inflammatory response in FLS. We found that roflumilast attenuated IL-18-induced oxidative stress by reducing the production of reactive oxygen species and malondialdehyde (MDA) in MH7A fibroblast-like synoviocytes (FLS). Additionally, roflumilast prevented IL-18-induced expressions and secretions of pro-inflammatory cytokines such as IL-6, IL-8, and TNF-α. Importantly, we found that roflumilast inhibited IL-18-induced expressions of chemokines such as CCL5, CXCL9, and CXCL10. Further, roflumilast inhibited the expression of extracellular matrix degradative enzymes, such as matrix metalloproteinase-3 (MMP-3) and MMP-13. Mechanistically, we found that roflumilast suppressed the activation of the transcriptional factor AP-1 and NF-κB. Our results suggest that roflumilast might be a potential therapeutic agent for the treatment of RA. American Chemical Society 2021-01-14 /pmc/articles/PMC7841938/ /pubmed/33521454 http://dx.doi.org/10.1021/acsomega.0c05281 Text en © 2021 American Chemical Society This is an open access article published under a Creative Commons Non-Commercial No Derivative Works (CC-BY-NC-ND) Attribution License (http://pubs.acs.org/page/policy/authorchoice_ccbyncnd_termsofuse.html) , which permits copying and redistribution of the article, and creation of adaptations, all for non-commercial purposes. |
spellingShingle | Zhong, Bing Guo, Shuanghong Yang, Zhongai Han, Li Du, Junsheng Chen, Jin Dun, Xianli Wang, Guangyong Roflumilast Reduced the IL-18-Induced Inflammatory Response in Fibroblast-Like Synoviocytes (FLS) |
title | Roflumilast Reduced the IL-18-Induced Inflammatory
Response in Fibroblast-Like Synoviocytes (FLS) |
title_full | Roflumilast Reduced the IL-18-Induced Inflammatory
Response in Fibroblast-Like Synoviocytes (FLS) |
title_fullStr | Roflumilast Reduced the IL-18-Induced Inflammatory
Response in Fibroblast-Like Synoviocytes (FLS) |
title_full_unstemmed | Roflumilast Reduced the IL-18-Induced Inflammatory
Response in Fibroblast-Like Synoviocytes (FLS) |
title_short | Roflumilast Reduced the IL-18-Induced Inflammatory
Response in Fibroblast-Like Synoviocytes (FLS) |
title_sort | roflumilast reduced the il-18-induced inflammatory
response in fibroblast-like synoviocytes (fls) |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841938/ https://www.ncbi.nlm.nih.gov/pubmed/33521454 http://dx.doi.org/10.1021/acsomega.0c05281 |
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