Multiple-Factors-Induced Rheumatoid Arthritis Synoviocyte Activation Is Attenuated by the α2-Adrenergic Receptor Agonist Dexmedetomidine
Dexmedetomidine (Dex) has analgesic and sedative properties and anti-inflammatory functions. Although the effects of Dex on arthritis have been revealed, the physiological mechanism underlying the interaction between Dex and rheumatoid arthritis (RA)-mediated inflammatory cytokines has not been full...
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Veröffentlicht in: | International journal of molecular sciences 2023-06, Vol.24 (13), p.10756 |
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description | Dexmedetomidine (Dex) has analgesic and sedative properties and anti-inflammatory functions. Although the effects of Dex on arthritis have been revealed, the physiological mechanism underlying the interaction between Dex and rheumatoid arthritis (RA)-mediated inflammatory cytokines has not been fully studied. Inflamed and migrated fibroblast-like synoviocytes (FLSs) are involved in RA severity. Thus, we aimed to determine the effects of Dex on RA-FLSs treated with inflammatory cytokines and a growth factor as multiple stimulating inputs. TNF-α, IL-6, and EGF as multiple stimulating inputs increased the cAMP concentration of RA-FLSs, while Dex treatment reduced cAMP concentration. Dex reduced electroneutral sodium-bicarbonate cotransporter 1 (NBCn1) expression, NBC activity, and subsequent RA-FLS migration. The mRNA expression levels of RA-related factors, such as inflammatory cytokines and osteoclastogenesis factors, were enhanced by multiple-input treatment. Notably, Dex effectively reduced these expression levels in RA-FLSs. These results indicate that multiple inflammatory or stimulating inputs enhance RA-FLS migration, and treatment with Dex relieves activated RA-FLSs, suggesting that Dex is a potential therapeutic drug for RA. |
doi_str_mv | 10.3390/ijms241310756 |
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Although the effects of Dex on arthritis have been revealed, the physiological mechanism underlying the interaction between Dex and rheumatoid arthritis (RA)-mediated inflammatory cytokines has not been fully studied. Inflamed and migrated fibroblast-like synoviocytes (FLSs) are involved in RA severity. Thus, we aimed to determine the effects of Dex on RA-FLSs treated with inflammatory cytokines and a growth factor as multiple stimulating inputs. TNF-α, IL-6, and EGF as multiple stimulating inputs increased the cAMP concentration of RA-FLSs, while Dex treatment reduced cAMP concentration. Dex reduced electroneutral sodium-bicarbonate cotransporter 1 (NBCn1) expression, NBC activity, and subsequent RA-FLS migration. The mRNA expression levels of RA-related factors, such as inflammatory cytokines and osteoclastogenesis factors, were enhanced by multiple-input treatment. Notably, Dex effectively reduced these expression levels in RA-FLSs. These results indicate that multiple inflammatory or stimulating inputs enhance RA-FLS migration, and treatment with Dex relieves activated RA-FLSs, suggesting that Dex is a potential therapeutic drug for RA.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms241310756</identifier><identifier>PMID: 37445932</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Adrenergic Agonists - pharmacology ; Adrenergic receptors ; Analgesics ; Arthritis ; Arthritis, Rheumatoid - metabolism ; Bicarbonates ; Carbonates ; Cell Movement ; Cell Proliferation ; Cells, Cultured ; Cyclic adenylic acid ; Cyclic AMP ; Cytokines ; Cytokines - metabolism ; Dexmedetomidine ; Dexmedetomidine - pharmacology ; Dexmedetomidine - therapeutic use ; Epidermal growth factor ; Ethylenediaminetetraacetic acid ; Fibroblasts - metabolism ; Gene expression ; Growth factors ; Humans ; Inflammation ; Interleukin 6 ; Kinases ; Localization ; Osteoclastogenesis ; Phosphorylation ; Physiological aspects ; Physiological effects ; Proteins ; Receptors (physiology) ; Rheumatoid arthritis ; Rheumatoid factor ; RNA ; Synoviocytes ; Synoviocytes - metabolism ; Tumor necrosis factor ; Tumor necrosis factor-α</subject><ispartof>International journal of molecular sciences, 2023-06, Vol.24 (13), p.10756</ispartof><rights>COPYRIGHT 2023 MDPI AG</rights><rights>2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2023 by the authors. 2023</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c439t-538efaef0bf35ae0dea7891d92a530ff26edd58083cf6ea78953f3fc953bff543</cites><orcidid>0000-0003-3623-2201 ; 0000-0003-1990-2533</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10341941/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10341941/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37445932$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, Dongun</creatorcontrib><creatorcontrib>Hong, Jeong Hee</creatorcontrib><title>Multiple-Factors-Induced Rheumatoid Arthritis Synoviocyte Activation Is Attenuated by the α2-Adrenergic Receptor Agonist Dexmedetomidine</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>Dexmedetomidine (Dex) has analgesic and sedative properties and anti-inflammatory functions. Although the effects of Dex on arthritis have been revealed, the physiological mechanism underlying the interaction between Dex and rheumatoid arthritis (RA)-mediated inflammatory cytokines has not been fully studied. Inflamed and migrated fibroblast-like synoviocytes (FLSs) are involved in RA severity. Thus, we aimed to determine the effects of Dex on RA-FLSs treated with inflammatory cytokines and a growth factor as multiple stimulating inputs. TNF-α, IL-6, and EGF as multiple stimulating inputs increased the cAMP concentration of RA-FLSs, while Dex treatment reduced cAMP concentration. Dex reduced electroneutral sodium-bicarbonate cotransporter 1 (NBCn1) expression, NBC activity, and subsequent RA-FLS migration. The mRNA expression levels of RA-related factors, such as inflammatory cytokines and osteoclastogenesis factors, were enhanced by multiple-input treatment. Notably, Dex effectively reduced these expression levels in RA-FLSs. These results indicate that multiple inflammatory or stimulating inputs enhance RA-FLS migration, and treatment with Dex relieves activated RA-FLSs, suggesting that Dex is a potential therapeutic drug for RA.</description><subject>Adrenergic Agonists - pharmacology</subject><subject>Adrenergic receptors</subject><subject>Analgesics</subject><subject>Arthritis</subject><subject>Arthritis, Rheumatoid - metabolism</subject><subject>Bicarbonates</subject><subject>Carbonates</subject><subject>Cell Movement</subject><subject>Cell Proliferation</subject><subject>Cells, Cultured</subject><subject>Cyclic adenylic acid</subject><subject>Cyclic AMP</subject><subject>Cytokines</subject><subject>Cytokines - metabolism</subject><subject>Dexmedetomidine</subject><subject>Dexmedetomidine - pharmacology</subject><subject>Dexmedetomidine - therapeutic use</subject><subject>Epidermal growth factor</subject><subject>Ethylenediaminetetraacetic acid</subject><subject>Fibroblasts - metabolism</subject><subject>Gene expression</subject><subject>Growth factors</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Interleukin 6</subject><subject>Kinases</subject><subject>Localization</subject><subject>Osteoclastogenesis</subject><subject>Phosphorylation</subject><subject>Physiological aspects</subject><subject>Physiological effects</subject><subject>Proteins</subject><subject>Receptors (physiology)</subject><subject>Rheumatoid arthritis</subject><subject>Rheumatoid factor</subject><subject>RNA</subject><subject>Synoviocytes</subject><subject>Synoviocytes - metabolism</subject><subject>Tumor necrosis factor</subject><subject>Tumor necrosis factor-α</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNptks1uEzEQxy1ERUvgyBVZ4sJlW6_t_TqhVUshUhFSgbPl2OPE0a4dbG9EHoHH4UV4Jpx-0SDkw1gzv_-MZvRH6FVJThnryJldj5HykpWkqeon6KTklBaE1M3TR_9j9DzGNSGU0ap7ho5Zw3nVMXqCfn6ahmQ3AxSXUiUfYjF3elKg8fUKplEmbzXuQ1oFm2zEX3bOb61XuwS4V8luZbLe4XnEfUrgJpmycrHDaQX49y9a9DqAg7C0Cl-Dgk2egPuldzYmfAE_RtCQ_Gi1dfACHRk5RHh5F2fo2-X7r-cfi6vPH-bn_VWhOOtSUbEWjARDFoZVEogG2bRdqTsqK0aMoTVoXbWkZcrUN7WKGWZUDgtjKs5m6N1t3820yPMVuBTkIDbBjjLshJdWHFacXYml34qSMF52-dQz9PauQ_DfJ4hJjDYqGAbpwE9R0Ja1lFNSdhl98w-69lNweb89VXNes5r9pZZyAGGd8Xmw2jcVfVO1rGx4RzN1-h8qPw2jVd6BsTl_IChuBSr4GAOYhyVLIvbmEQfmyfzrx5d5oO_dwv4AhrfDUA</recordid><startdate>20230628</startdate><enddate>20230628</enddate><creator>Lee, Dongun</creator><creator>Hong, Jeong Hee</creator><general>MDPI AG</general><general>MDPI</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-3623-2201</orcidid><orcidid>https://orcid.org/0000-0003-1990-2533</orcidid></search><sort><creationdate>20230628</creationdate><title>Multiple-Factors-Induced Rheumatoid Arthritis Synoviocyte Activation Is Attenuated by the α2-Adrenergic Receptor Agonist Dexmedetomidine</title><author>Lee, Dongun ; Hong, Jeong Hee</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c439t-538efaef0bf35ae0dea7891d92a530ff26edd58083cf6ea78953f3fc953bff543</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Adrenergic Agonists - pharmacology</topic><topic>Adrenergic receptors</topic><topic>Analgesics</topic><topic>Arthritis</topic><topic>Arthritis, Rheumatoid - metabolism</topic><topic>Bicarbonates</topic><topic>Carbonates</topic><topic>Cell Movement</topic><topic>Cell Proliferation</topic><topic>Cells, Cultured</topic><topic>Cyclic adenylic acid</topic><topic>Cyclic AMP</topic><topic>Cytokines</topic><topic>Cytokines - metabolism</topic><topic>Dexmedetomidine</topic><topic>Dexmedetomidine - pharmacology</topic><topic>Dexmedetomidine - therapeutic use</topic><topic>Epidermal growth factor</topic><topic>Ethylenediaminetetraacetic acid</topic><topic>Fibroblasts - metabolism</topic><topic>Gene expression</topic><topic>Growth factors</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Interleukin 6</topic><topic>Kinases</topic><topic>Localization</topic><topic>Osteoclastogenesis</topic><topic>Phosphorylation</topic><topic>Physiological aspects</topic><topic>Physiological effects</topic><topic>Proteins</topic><topic>Receptors (physiology)</topic><topic>Rheumatoid arthritis</topic><topic>Rheumatoid factor</topic><topic>RNA</topic><topic>Synoviocytes</topic><topic>Synoviocytes - metabolism</topic><topic>Tumor necrosis factor</topic><topic>Tumor necrosis factor-α</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lee, Dongun</creatorcontrib><creatorcontrib>Hong, Jeong Hee</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>International journal of molecular sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lee, Dongun</au><au>Hong, Jeong Hee</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Multiple-Factors-Induced Rheumatoid Arthritis Synoviocyte Activation Is Attenuated by the α2-Adrenergic Receptor Agonist Dexmedetomidine</atitle><jtitle>International journal of molecular sciences</jtitle><addtitle>Int J Mol Sci</addtitle><date>2023-06-28</date><risdate>2023</risdate><volume>24</volume><issue>13</issue><spage>10756</spage><pages>10756-</pages><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><abstract>Dexmedetomidine (Dex) has analgesic and sedative properties and anti-inflammatory functions. Although the effects of Dex on arthritis have been revealed, the physiological mechanism underlying the interaction between Dex and rheumatoid arthritis (RA)-mediated inflammatory cytokines has not been fully studied. Inflamed and migrated fibroblast-like synoviocytes (FLSs) are involved in RA severity. Thus, we aimed to determine the effects of Dex on RA-FLSs treated with inflammatory cytokines and a growth factor as multiple stimulating inputs. TNF-α, IL-6, and EGF as multiple stimulating inputs increased the cAMP concentration of RA-FLSs, while Dex treatment reduced cAMP concentration. Dex reduced electroneutral sodium-bicarbonate cotransporter 1 (NBCn1) expression, NBC activity, and subsequent RA-FLS migration. The mRNA expression levels of RA-related factors, such as inflammatory cytokines and osteoclastogenesis factors, were enhanced by multiple-input treatment. Notably, Dex effectively reduced these expression levels in RA-FLSs. These results indicate that multiple inflammatory or stimulating inputs enhance RA-FLS migration, and treatment with Dex relieves activated RA-FLSs, suggesting that Dex is a potential therapeutic drug for RA.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>37445932</pmid><doi>10.3390/ijms241310756</doi><orcidid>https://orcid.org/0000-0003-3623-2201</orcidid><orcidid>https://orcid.org/0000-0003-1990-2533</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Adrenergic Agonists - pharmacology Adrenergic receptors Analgesics Arthritis Arthritis, Rheumatoid - metabolism Bicarbonates Carbonates Cell Movement Cell Proliferation Cells, Cultured Cyclic adenylic acid Cyclic AMP Cytokines Cytokines - metabolism Dexmedetomidine Dexmedetomidine - pharmacology Dexmedetomidine - therapeutic use Epidermal growth factor Ethylenediaminetetraacetic acid Fibroblasts - metabolism Gene expression Growth factors Humans Inflammation Interleukin 6 Kinases Localization Osteoclastogenesis Phosphorylation Physiological aspects Physiological effects Proteins Receptors (physiology) Rheumatoid arthritis Rheumatoid factor RNA Synoviocytes Synoviocytes - metabolism Tumor necrosis factor Tumor necrosis factor-α |
title | Multiple-Factors-Induced Rheumatoid Arthritis Synoviocyte Activation Is Attenuated by the α2-Adrenergic Receptor Agonist Dexmedetomidine |
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