Utilize este identificador para referenciar este registo:
https://hdl.handle.net/1822/57992
Título: | Adrenoceptor-stimulated inflammatory response in stress-induced serum amyloid A synthesis |
Autor(es): | Konstandi, Maria Sotiropoulos, I. Matsubara, Tsutomu Malliou, Foteini Katsogridaki, Alexandra Andriopoulou, Christina E. Gonzalez, Frank J. |
Palavras-chave: | Adrenoceptors IL-1β IL-6 SAA1/2 SAA3 Stress TNFα SAA1 2 IL-1 beta |
Data: | 6-Jan-2019 |
Editora: | Springer Verlag |
Revista: | Psychopharmacology |
Resumo(s): | 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. |
Tipo: | Artigo |
URI: | https://hdl.handle.net/1822/57992 |
DOI: | 10.1007/s00213-018-5149-4 |
ISSN: | 0033-3158 |
e-ISSN: | 1432-2072 |
Versão da editora: | https://link.springer.com/content/pdf/10.1007/s00213-018-5149-4.pdf |
Arbitragem científica: | yes |
Acesso: | Acesso aberto |
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 |