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IL-38 and IL-36 Target Autophagy for Regulating Synoviocyte Proliferation, Migration, and Invasion in Rheumatoid Arthritis
Rheumatoid arthritis (RA) is an autoimmune disease leading to severe joint damage and disability. Fibroblast-like synoviocytes (FLSs) mostly contribute to the joint inflammation and destruction in RA through distinct mechanisms. However, little is known about newly discovered interleukin- (IL-) 36 a...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8627363/ https://www.ncbi.nlm.nih.gov/pubmed/34845417 http://dx.doi.org/10.1155/2021/7933453 |
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author | Hao, Zhe Liu, Yi |
author_facet | Hao, Zhe Liu, Yi |
author_sort | Hao, Zhe |
collection | PubMed |
description | Rheumatoid arthritis (RA) is an autoimmune disease leading to severe joint damage and disability. Fibroblast-like synoviocytes (FLSs) mostly contribute to the joint inflammation and destruction in RA through distinct mechanisms. However, little is known about newly discovered interleukin- (IL-) 36 and IL-38 involving in the pathology of RA. Here, we assessed the effect of IL-36 and IL-38 on RA-FLS function using IL-36 and IL-38 overexpression plasmids. We found that IL-36 inhibited synoviocytes proliferation while IL-38 showed an opposite influence. Furthermore, IL-36 and IL-38 significantly sequestered or accelerated RA-FLS migration and invasion capacity, respectively. Mechanically, IL-36 and IL-38 targeted autophagy for RA-FLS modulation. Using autophagy inhibitor 3-MA and inducer compound rapamycin, we found that autophagy negatively regulated the survival, migration, and invasion of synovial cells. Based on these results, IL-38 in combination with autophagy inhibitor 3-MA treatment demonstrated the strongest blockage of the above three activities of RA-FLS, and IL-38 overexpression reversed rapamycin-inhibited cell proliferation, migration, and invasion. Moreover, injection of IL-36 can improve the symptoms of RA in a rat model of RA. Taken together, we conclude that IL-38 and IL-36 target autophagy for regulating synoviocyte proliferation, migration, and invasion in RA. |
format | Online Article Text |
id | pubmed-8627363 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-86273632021-11-28 IL-38 and IL-36 Target Autophagy for Regulating Synoviocyte Proliferation, Migration, and Invasion in Rheumatoid Arthritis Hao, Zhe Liu, Yi Dis Markers Research Article Rheumatoid arthritis (RA) is an autoimmune disease leading to severe joint damage and disability. Fibroblast-like synoviocytes (FLSs) mostly contribute to the joint inflammation and destruction in RA through distinct mechanisms. However, little is known about newly discovered interleukin- (IL-) 36 and IL-38 involving in the pathology of RA. Here, we assessed the effect of IL-36 and IL-38 on RA-FLS function using IL-36 and IL-38 overexpression plasmids. We found that IL-36 inhibited synoviocytes proliferation while IL-38 showed an opposite influence. Furthermore, IL-36 and IL-38 significantly sequestered or accelerated RA-FLS migration and invasion capacity, respectively. Mechanically, IL-36 and IL-38 targeted autophagy for RA-FLS modulation. Using autophagy inhibitor 3-MA and inducer compound rapamycin, we found that autophagy negatively regulated the survival, migration, and invasion of synovial cells. Based on these results, IL-38 in combination with autophagy inhibitor 3-MA treatment demonstrated the strongest blockage of the above three activities of RA-FLS, and IL-38 overexpression reversed rapamycin-inhibited cell proliferation, migration, and invasion. Moreover, injection of IL-36 can improve the symptoms of RA in a rat model of RA. Taken together, we conclude that IL-38 and IL-36 target autophagy for regulating synoviocyte proliferation, migration, and invasion in RA. Hindawi 2021-11-20 /pmc/articles/PMC8627363/ /pubmed/34845417 http://dx.doi.org/10.1155/2021/7933453 Text en Copyright © 2021 Zhe Hao and Yi Liu. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Hao, Zhe Liu, Yi IL-38 and IL-36 Target Autophagy for Regulating Synoviocyte Proliferation, Migration, and Invasion in Rheumatoid Arthritis |
title | IL-38 and IL-36 Target Autophagy for Regulating Synoviocyte Proliferation, Migration, and Invasion in Rheumatoid Arthritis |
title_full | IL-38 and IL-36 Target Autophagy for Regulating Synoviocyte Proliferation, Migration, and Invasion in Rheumatoid Arthritis |
title_fullStr | IL-38 and IL-36 Target Autophagy for Regulating Synoviocyte Proliferation, Migration, and Invasion in Rheumatoid Arthritis |
title_full_unstemmed | IL-38 and IL-36 Target Autophagy for Regulating Synoviocyte Proliferation, Migration, and Invasion in Rheumatoid Arthritis |
title_short | IL-38 and IL-36 Target Autophagy for Regulating Synoviocyte Proliferation, Migration, and Invasion in Rheumatoid Arthritis |
title_sort | il-38 and il-36 target autophagy for regulating synoviocyte proliferation, migration, and invasion in rheumatoid arthritis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8627363/ https://www.ncbi.nlm.nih.gov/pubmed/34845417 http://dx.doi.org/10.1155/2021/7933453 |
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