G protein-coupled receptor kinase 5 deletion suppresses synovial inflammation in a murine model of collagen antibody-induced arthritis

Abstract G protein-coupled receptor kinase 5 (GRK5) regulates inflammatory responses via the nuclear factor-kappa B (NF-κB) pathway. This study investigated the functional involvement of GRK5 in the pathogenesis of inflammatory arthritis. Immunohistochemically, rheumatoid arthritis (RA) synovium had...

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Autores principales:	Masakazu Toya, Yukio Akasaki, Takuya Sueishi, Ichiro Kurakazu, Masanari Kuwahara, Taisuke Uchida, Tomoaki Tsutsui, Hidetoshi Tsushima, Hisakata Yamada, Martin K. Lotz, Yasuharu Nakashima
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2638c7ea22824548af6160da54e5d45a
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spelling	oai:doaj.org-article:2638c7ea22824548af6160da54e5d45a2021-12-02T16:51:20ZG protein-coupled receptor kinase 5 deletion suppresses synovial inflammation in a murine model of collagen antibody-induced arthritis10.1038/s41598-021-90020-02045-2322https://doaj.org/article/2638c7ea22824548af6160da54e5d45a2021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90020-0https://doaj.org/toc/2045-2322Abstract G protein-coupled receptor kinase 5 (GRK5) regulates inflammatory responses via the nuclear factor-kappa B (NF-κB) pathway. This study investigated the functional involvement of GRK5 in the pathogenesis of inflammatory arthritis. Immunohistochemically, rheumatoid arthritis (RA) synovium had a significantly higher proportion of GRK5-positive cells in the synovial lining layer than healthy control synovium. Gene expression and NF-κB activation in lipopolysaccharide-stimulated human SW982 synovial cells were significantly suppressed by silencing of the GRK5 gene. Similarly, GRK5 kinase activity inhibition in human primary RA synovial cells attenuated gene expressions of inflammatory factors. In a murine model of collagen antibody-induced arthritis, arthritis scores and serum IL6 production of GRK5 knockout (GRK5-/-) mice were significantly lower than those of wild-type mice. Histologically, the degree of synovitis and cartilage degeneration in GRK5-/- mice was significantly lower than in wild-type mice. In in vitro analyses using activated murine macrophages and fibroblast-like synoviocytes, gene expression of inflammatory factors and p65 nuclear translocation were significantly lower in GRK5-/- mice compared to wild-type mice. In conclusion, our results suggested that GRK5 is deeply involved in the pathogenesis of inflammatory arthritis, therefore, GRK5 inhibition could be a potential therapeutic target for types of inflammatory arthritis such as RA.Masakazu ToyaYukio AkasakiTakuya SueishiIchiro KurakazuMasanari KuwaharaTaisuke UchidaTomoaki TsutsuiHidetoshi TsushimaHisakata YamadaMartin K. LotzYasuharu NakashimaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Masakazu Toya Yukio Akasaki Takuya Sueishi Ichiro Kurakazu Masanari Kuwahara Taisuke Uchida Tomoaki Tsutsui Hidetoshi Tsushima Hisakata Yamada Martin K. Lotz Yasuharu Nakashima G protein-coupled receptor kinase 5 deletion suppresses synovial inflammation in a murine model of collagen antibody-induced arthritis
description	Abstract G protein-coupled receptor kinase 5 (GRK5) regulates inflammatory responses via the nuclear factor-kappa B (NF-κB) pathway. This study investigated the functional involvement of GRK5 in the pathogenesis of inflammatory arthritis. Immunohistochemically, rheumatoid arthritis (RA) synovium had a significantly higher proportion of GRK5-positive cells in the synovial lining layer than healthy control synovium. Gene expression and NF-κB activation in lipopolysaccharide-stimulated human SW982 synovial cells were significantly suppressed by silencing of the GRK5 gene. Similarly, GRK5 kinase activity inhibition in human primary RA synovial cells attenuated gene expressions of inflammatory factors. In a murine model of collagen antibody-induced arthritis, arthritis scores and serum IL6 production of GRK5 knockout (GRK5-/-) mice were significantly lower than those of wild-type mice. Histologically, the degree of synovitis and cartilage degeneration in GRK5-/- mice was significantly lower than in wild-type mice. In in vitro analyses using activated murine macrophages and fibroblast-like synoviocytes, gene expression of inflammatory factors and p65 nuclear translocation were significantly lower in GRK5-/- mice compared to wild-type mice. In conclusion, our results suggested that GRK5 is deeply involved in the pathogenesis of inflammatory arthritis, therefore, GRK5 inhibition could be a potential therapeutic target for types of inflammatory arthritis such as RA.
format	article
author	Masakazu Toya Yukio Akasaki Takuya Sueishi Ichiro Kurakazu Masanari Kuwahara Taisuke Uchida Tomoaki Tsutsui Hidetoshi Tsushima Hisakata Yamada Martin K. Lotz Yasuharu Nakashima
author_facet	Masakazu Toya Yukio Akasaki Takuya Sueishi Ichiro Kurakazu Masanari Kuwahara Taisuke Uchida Tomoaki Tsutsui Hidetoshi Tsushima Hisakata Yamada Martin K. Lotz Yasuharu Nakashima
author_sort	Masakazu Toya
title	G protein-coupled receptor kinase 5 deletion suppresses synovial inflammation in a murine model of collagen antibody-induced arthritis
title_short	G protein-coupled receptor kinase 5 deletion suppresses synovial inflammation in a murine model of collagen antibody-induced arthritis
title_full	G protein-coupled receptor kinase 5 deletion suppresses synovial inflammation in a murine model of collagen antibody-induced arthritis
title_fullStr	G protein-coupled receptor kinase 5 deletion suppresses synovial inflammation in a murine model of collagen antibody-induced arthritis
title_full_unstemmed	G protein-coupled receptor kinase 5 deletion suppresses synovial inflammation in a murine model of collagen antibody-induced arthritis
title_sort	g protein-coupled receptor kinase 5 deletion suppresses synovial inflammation in a murine model of collagen antibody-induced arthritis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/2638c7ea22824548af6160da54e5d45a
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G protein-coupled receptor kinase 5 deletion suppresses synovial inflammation in a murine model of collagen antibody-induced arthritis

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