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...

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Autores principales:	Zhe Hao, Yi Liu
Formato:	article
Lenguaje:	EN
Publicado:	Hindawi Limited 2021
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/d9f18565341048699787bc2657da6835
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spelling	oai:doaj.org-article:d9f18565341048699787bc2657da68352021-11-29T00:57:12ZIL-38 and IL-36 Target Autophagy for Regulating Synoviocyte Proliferation, Migration, and Invasion in Rheumatoid Arthritis1875-863010.1155/2021/7933453https://doaj.org/article/d9f18565341048699787bc2657da68352021-01-01T00:00:00Zhttp://dx.doi.org/10.1155/2021/7933453https://doaj.org/toc/1875-8630Rheumatoid 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.Zhe HaoYi LiuHindawi LimitedarticleMedicine (General)R5-920ENDisease Markers, Vol 2021 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Zhe Hao Yi Liu IL-38 and IL-36 Target Autophagy for Regulating Synoviocyte Proliferation, Migration, and Invasion in Rheumatoid Arthritis
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	article
author	Zhe Hao Yi Liu
author_facet	Zhe Hao Yi Liu
author_sort	Zhe Hao
title	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_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_sort	il-38 and il-36 target autophagy for regulating synoviocyte proliferation, migration, and invasion in rheumatoid arthritis
publisher	Hindawi Limited
publishDate	2021
url	https://doaj.org/article/d9f18565341048699787bc2657da6835
work_keys_str_mv	AT zhehao il38andil36targetautophagyforregulatingsynoviocyteproliferationmigrationandinvasioninrheumatoidarthritis AT yiliu il38andil36targetautophagyforregulatingsynoviocyteproliferationmigrationandinvasioninrheumatoidarthritis
_version_	1718407676475473920

IL-38 and IL-36 Target Autophagy for Regulating Synoviocyte Proliferation, Migration, and Invasion in Rheumatoid Arthritis

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