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https://hdl.handle.net/1822/57992
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Campo DC | Valor | Idioma |
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dc.contributor.author | Konstandi, Maria | por |
dc.contributor.author | Sotiropoulos, I. | por |
dc.contributor.author | Matsubara, Tsutomu | por |
dc.contributor.author | Malliou, Foteini | por |
dc.contributor.author | Katsogridaki, Alexandra | por |
dc.contributor.author | Andriopoulou, Christina E. | por |
dc.contributor.author | Gonzalez, Frank J. | por |
dc.date.accessioned | 2019-01-09T17:26:55Z | - |
dc.date.available | 2020-01-06T07:00:21Z | - |
dc.date.issued | 2019-01-06 | - |
dc.identifier.issn | 0033-3158 | - |
dc.identifier.uri | https://hdl.handle.net/1822/57992 | - |
dc.description.abstract | Rationale Stressful life events are suggested to contribute to the development of various pathologies, such as cardiovascular disorders, whose etiopathogenesis is highly associated with elevated levels of serum amyloid A (SAA) proteins. SAA synthesis inthe liver isregulated bya complex network ofcytokines actingindependently orinconcert withvarious hormones/stimulants including the stress-activated sympathetic nervous system. Objective This study aims to investigate the underlying mechanisms that regulate the stress-induced hepatic synthesis of SAA, with particular focus on adrenoceptors (AR), major components of the sympathoadrenal response to stress. Methods and results We demonstrated that repeated stress elevates IL-1β, IL-6, and TNFα serum levels in mice, accompanied by increased synthesis and secretion of hepatic SAA1/2 and SAA3, an effect that was blocked by AR antagonists. Moreover, stimulation ofα1- andβ1/2-ARsmimics thestress effectonSAA1/2 regulation, whereas α2-AR stimulation exhibitsa relatively weakimpactonSAA.InsupportoftheessentialcytokinecontributionintheAR-agonistinducedSAAproductionisthefactthat theanti-inflammatorydrug,sodiumsalicylate,preventedtheAR-stimulatedhepaticSAA1/2synthesisbyreducingIL-1βlevels, whereasIL-1βinhibitionwithAnakinramimicsthissodiumsalicylatepreventiveeffect,thusindicatingacrucial rolefor IL-1β. Interestingly, the AR-driven SAA3 synthesis was elevated by sodium salicylate in a TNFα-dependent way, supporting diverse and complex regulatory roles of cytokines in SAA production. In contrast to α1/α2-AR, the β1/2-AR-mediated SAA1/2 and SAA3 upregulation cannot be reversed by fenofibrate, a hypolipidemic drug with anti-inflammatory properties. Conclusion Taken together, these findings strongly support a critical role of the AR-stimulated inflammatory response in the hepatic SAA production under stressful conditions, highlighting distinct AR type-specific mechanisms that regulate the hepatic synthesis of SAA1/2 and SAA3. | por |
dc.description.sponsorship | This research was supported by the European Union (European Regional Development Fund-ERDF) and the Greek national funds through the Operational Program "THESSALY-MAINLAND GREECE AND EPIRUS-2007-2013" of the National Strategic Reference Framework (NSRF 2007-2013, Grant 346985/80753) and the National Cancer Institute Intramural Research Program. | por |
dc.language.iso | eng | por |
dc.publisher | Springer Verlag | por |
dc.rights | openAccess | por |
dc.subject | Adrenoceptors | por |
dc.subject | IL-1β | por |
dc.subject | IL-6 | por |
dc.subject | SAA1/2 | por |
dc.subject | SAA3 | por |
dc.subject | Stress | por |
dc.subject | TNFα | por |
dc.subject | SAA1 | por |
dc.subject | 2 | por |
dc.subject | IL-1 beta | por |
dc.title | Adrenoceptor-stimulated inflammatory response in stress-induced serum amyloid A synthesis | por |
dc.type | article | por |
dc.peerreviewed | yes | por |
dc.relation.publisherversion | https://link.springer.com/content/pdf/10.1007/s00213-018-5149-4.pdf | por |
oaire.citationStartPage | 1687 | por |
oaire.citationEndPage | 1699 | por |
oaire.citationIssue | 6 | por |
oaire.citationVolume | 236 | por |
dc.identifier.eissn | 1432-2072 | - |
dc.identifier.doi | 10.1007/s00213-018-5149-4 | por |
dc.identifier.pmid | 30612190 | por |
dc.subject.fos | Ciências Médicas::Medicina Básica | por |
dc.description.publicationversion | info:eu-repo/semantics/publishedVersion | por |
dc.subject.wos | Science & Technology | por |
sdum.journal | Psychopharmacology | por |
Aparece nas coleções: | ICVS - Artigos em revistas internacionais / Papers in international journals |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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Konstandi2019_Article_Adrenoceptor-stimulatedInflamm vCT.pdf | 1,22 MB | Adobe PDF | Ver/Abrir |