Publicação
Adrenoceptor-stimulated inflammatory response in stress-induced serum amyloid A synthesis
| Resumo: | 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. |
|---|---|
| Autores principais: | Konstandi, Maria |
| Outros Autores: | Sotiropoulos, I.; Matsubara, Tsutomu; Malliou, Foteini; Katsogridaki, Alexandra; Andriopoulou, Christina E.; Gonzalez, Frank J. |
| Assunto: | Adrenoceptors IL-1β IL-6 SAA1/2 SAA3 Stress TNFα SAA1 2 IL-1 beta Ciências Médicas::Medicina Básica |
| Ano: | 2019 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade do Minho |
| Idioma: | inglês |
| Origem: | RepositóriUM - Universidade do Minho |
| _version_ | 1867439834157547520 |
|---|---|
| author | Konstandi, Maria |
| author2 | Sotiropoulos, I. Matsubara, Tsutomu Malliou, Foteini Katsogridaki, Alexandra Andriopoulou, Christina E. Gonzalez, Frank J. |
| author2_role | author author author author author author |
| author_facet | Konstandi, Maria Sotiropoulos, I. Matsubara, Tsutomu Malliou, Foteini Katsogridaki, Alexandra Andriopoulou, Christina E. Gonzalez, Frank J. |
| author_role | author |
| contributor_name_str_mv | RepositóriUM - Universidade do Minho |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Konstandi, Maria\"},{\"Person.name\":\"Sotiropoulos, I.\"},{\"Person.name\":\"Matsubara, Tsutomu\"},{\"Person.name\":\"Malliou, Foteini\"},{\"Person.name\":\"Katsogridaki, Alexandra\"},{\"Person.name\":\"Andriopoulou, Christina E.\"},{\"Person.name\":\"Gonzalez, Frank J.\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | RepositóriUM - Universidade do Minho |
| datacite.creators.creator.creatorName.fl_str_mv | Konstandi, Maria Sotiropoulos, I. Matsubara, Tsutomu Malliou, Foteini Katsogridaki, Alexandra Andriopoulou, Christina E. Gonzalez, Frank J. |
| datacite.date.Accepted.fl_str_mv | 2019-01-06T00:00:00Z |
| datacite.date.available.fl_str_mv | 2020-01-06T07:00:21Z |
| datacite.date.embargoed.fl_str_mv | 2020-01-06T07:00:21Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.subjects.subject.fl_str_mv | Adrenoceptors IL-1β IL-6 SAA1/2 SAA3 Stress TNFα SAA1 2 IL-1 beta Ciências Médicas::Medicina Básica |
| datacite.titles.title.fl_str_mv | Adrenoceptor-stimulated inflammatory response in stress-induced serum amyloid A synthesis |
| dc.contributor.none.fl_str_mv | RepositóriUM - Universidade do Minho |
| dc.creator.none.fl_str_mv | Konstandi, Maria Sotiropoulos, I. Matsubara, Tsutomu Malliou, Foteini Katsogridaki, Alexandra Andriopoulou, Christina E. Gonzalez, Frank J. |
| dc.date.Accepted.fl_str_mv | 2019-01-06T00:00:00Z |
| dc.date.available.fl_str_mv | 2020-01-06T07:00:21Z |
| dc.date.embargoed.fl_str_mv | 2020-01-06T07:00:21Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | https://hdl.handle.net/1822/57992 |
| dc.language.none.fl_str_mv | eng |
| dc.publisher.none.fl_str_mv | Springer Verlag |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.subject.none.fl_str_mv | Adrenoceptors IL-1β IL-6 SAA1/2 SAA3 Stress TNFα SAA1 2 IL-1 beta Ciências Médicas::Medicina Básica |
| dc.title.fl_str_mv | Adrenoceptor-stimulated inflammatory response in stress-induced serum amyloid A synthesis |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_6501 |
| description | 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. |
| dirty | 0 |
| eu_rights_str_mv | openAccess |
| format | article |
| fulltext.url.fl_str_mv | https://repositorium.uminho.pt/bitstreams/4b4b6f5d-b09b-4508-96a7-74655ce49801/download |
| id | rum_6de4fdfd4980020f2501b0ff92bf5f01 |
| identifier.url.fl_str_mv | https://hdl.handle.net/1822/57992 |
| instacron_str | repositorium |
| institution | Universidade do Minho |
| instname_str | Universidade do Minho |
| language | eng |
| network_acronym_str | rum |
| network_name_str | RepositóriUM - Universidade do Minho |
| oai_identifier_str | oai:repositorium.uminho.pt:1822/57992 |
| organization_str_mv | urn:organizationAcronym:repositorium |
| person_str_mv | Konstandi, Maria Sotiropoulos, I. Matsubara, Tsutomu Malliou, Foteini Katsogridaki, Alexandra Andriopoulou, Christina E. Gonzalez, Frank J. |
| publishDate | 2019 |
| publisher.none.fl_str_mv | Springer Verlag |
| reponame_str | RepositóriUM - Universidade do Minho |
| repository_id_str | urn:repositoryAcronym:rum |
| service_str_mv | urn:repositoryAcronym:rum |
| spelling | engSpringer VerlagporRationale 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.application/pdfporAdrenoceptor-stimulated inflammatory response in stress-induced serum amyloid A synthesisKonstandi, MariaSotiropoulos, I.Matsubara, TsutomuMalliou, FoteiniKatsogridaki, AlexandraAndriopoulou, Christina E.Gonzalez, Frank J.HostingInstitutionOrganizationalRepositóriUM - Universidade do Minhoe-mailmailto:repositorium@usdb.uminho.ptrepositorium@usdb.uminho.ptPMID30612190ISSNIsPartOf0033-3158EISSNIsPartOf1432-2072DOIIsPartOf10.1007/s00213-018-5149-42020-01-06T07:00:21Z2019-01-062019-01-06T00:00:00ZHandlehttps://hdl.handle.net/1822/57992http://purl.org/coar/access_right/c_abf2open accessAdrenoceptorsIL-1βIL-6SAA1/2SAA3StressTNFαSAA12IL-1 betahttp://www.oecd.org/science/inno/38235147.pdfFields of Science and Technology (FOS)Ciências Médicas::Medicina Básica1251909 bytesliteraturehttp://purl.org/coar/resource_type/c_6501journal articlehttp://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://repositorium.uminho.pt/bitstreams/4b4b6f5d-b09b-4508-96a7-74655ce49801/download |
| spellingShingle | Adrenoceptor-stimulated inflammatory response in stress-induced serum amyloid A synthesis Konstandi, Maria Adrenoceptors IL-1β IL-6 SAA1/2 SAA3 Stress TNFα SAA1 2 IL-1 beta Ciências Médicas::Medicina Básica |
| status | SINGLETON |
| subject.fl_str_mv | Adrenoceptors IL-1β IL-6 SAA1/2 SAA3 Stress TNFα SAA1 2 IL-1 beta |
| subject.other.fl_str_mv | Ciências Médicas::Medicina Básica |
| title | Adrenoceptor-stimulated inflammatory response in stress-induced serum amyloid A synthesis |
| title_full | Adrenoceptor-stimulated inflammatory response in stress-induced serum amyloid A synthesis |
| title_fullStr | Adrenoceptor-stimulated inflammatory response in stress-induced serum amyloid A synthesis |
| title_full_unstemmed | Adrenoceptor-stimulated inflammatory response in stress-induced serum amyloid A synthesis |
| title_short | Adrenoceptor-stimulated inflammatory response in stress-induced serum amyloid A synthesis |
| title_sort | Adrenoceptor-stimulated inflammatory response in stress-induced serum amyloid A synthesis |
| topic | Adrenoceptors IL-1β IL-6 SAA1/2 SAA3 Stress TNFα SAA1 2 IL-1 beta Ciências Médicas::Medicina Básica |
| topic_facet | Adrenoceptors IL-1β IL-6 SAA1/2 SAA3 Stress TNFα SAA1 2 IL-1 beta Ciências Médicas::Medicina Básica |
| url | https://hdl.handle.net/1822/57992 |
| visible | 1 |