Papel do sistema purinérgico no lúpus eritematoso sistêmico: um estudo clínico e de revisão
Autor(a) principal: | |
---|---|
Data de Publicação: | 2018 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Repositório Institucional Manancial UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/16489 |
Resumo: | Systemic Lupus Erythematosus (SLE) is a multifactorial inflammatory autoimmune disease caused by an immune dysfunction characterized by a breakdown of immune self-tolerance, activation of autoreactive T lymphocytes and B lymphocyte hyperactivity. The nucleotides and nucleoside adenine, such as ATP and adenosine, are key components in inflammatory and immune processes, including the modulation of lymphocyte functions. Their extracellular levels are regulated by ectoenzymes such as E-NTPDase which hydrolyzes ATP / ADP to AMP; E-5'-nucleotidase that degrades AMP to adenosine and E-adenosine deaminase (E-ADA) that converts adenosine to inosine. In this work, we determined the activity and expression of E-NTPDase, E-5'-nucleotidase expression, and E-ADA activity in lymphocytes, as well as ADA activity and nucleotide and nucleoside concentration in the serum of SLE patients. We also aimed to fill in some gaps we observed in the literature by writing a review article regarding purinergic signaling and SLE. Thirty-five patients from the University Hospital of Santa Maria (HUSM) with a diagnosis of SLE were selected, based on the Systemic Lupus International Collaborating Clinics (SLICC) classification criteria and 30 controls, from which blood samples were collected for the analyzes. The results showed an increase in the serum ATP concentration, possibly as a result of inflammation, and a decrease in adenosine levels in SLE patients. Increased activity (31%) and expression (37%) of E-NTPDase were observed in lymphocytes of SLE patients. The activity of E-ADA was also increased by approximately 42% in the lymphocytes of these patients. The serum ADA activity was reduced by 57%. Regarding the expression of E-5'-nucleotidase in lymphocytes of patients with SLE, no differences were observed. The increase observed in the activity and expression of E-NTPDase could represent a mechanism to help in the control of inflammation, since this enzyme exerts anti-inflammatory effects through the removal of ATP. However, increased E-ADA activity in lymphocytes could favor a Th1 response and limit the anti-inflammatory effects of adenosine. On the other hand, serum ADA has been shown to be decreased due to the impaired macrophage function present in these patients since most of the serum ADA comes from these cells. When we checked a gap in the literature regarding purinergic signaling and SLE, we decided to write a review on the topic to elucidate the effects of ATP and E-NTPDase on SLE and contribute to the understanding of SLE in this context. In view of this, we conclude that the NTPDase, ADA and the purinergic pathway play an important role in modulating the immune and inflammatory response in SLE patients. |
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2019-05-08T19:24:19Z2019-05-08T19:24:19Z2018-12-18http://repositorio.ufsm.br/handle/1/16489Systemic Lupus Erythematosus (SLE) is a multifactorial inflammatory autoimmune disease caused by an immune dysfunction characterized by a breakdown of immune self-tolerance, activation of autoreactive T lymphocytes and B lymphocyte hyperactivity. The nucleotides and nucleoside adenine, such as ATP and adenosine, are key components in inflammatory and immune processes, including the modulation of lymphocyte functions. Their extracellular levels are regulated by ectoenzymes such as E-NTPDase which hydrolyzes ATP / ADP to AMP; E-5'-nucleotidase that degrades AMP to adenosine and E-adenosine deaminase (E-ADA) that converts adenosine to inosine. In this work, we determined the activity and expression of E-NTPDase, E-5'-nucleotidase expression, and E-ADA activity in lymphocytes, as well as ADA activity and nucleotide and nucleoside concentration in the serum of SLE patients. We also aimed to fill in some gaps we observed in the literature by writing a review article regarding purinergic signaling and SLE. Thirty-five patients from the University Hospital of Santa Maria (HUSM) with a diagnosis of SLE were selected, based on the Systemic Lupus International Collaborating Clinics (SLICC) classification criteria and 30 controls, from which blood samples were collected for the analyzes. The results showed an increase in the serum ATP concentration, possibly as a result of inflammation, and a decrease in adenosine levels in SLE patients. Increased activity (31%) and expression (37%) of E-NTPDase were observed in lymphocytes of SLE patients. The activity of E-ADA was also increased by approximately 42% in the lymphocytes of these patients. The serum ADA activity was reduced by 57%. Regarding the expression of E-5'-nucleotidase in lymphocytes of patients with SLE, no differences were observed. The increase observed in the activity and expression of E-NTPDase could represent a mechanism to help in the control of inflammation, since this enzyme exerts anti-inflammatory effects through the removal of ATP. However, increased E-ADA activity in lymphocytes could favor a Th1 response and limit the anti-inflammatory effects of adenosine. On the other hand, serum ADA has been shown to be decreased due to the impaired macrophage function present in these patients since most of the serum ADA comes from these cells. When we checked a gap in the literature regarding purinergic signaling and SLE, we decided to write a review on the topic to elucidate the effects of ATP and E-NTPDase on SLE and contribute to the understanding of SLE in this context. In view of this, we conclude that the NTPDase, ADA and the purinergic pathway play an important role in modulating the immune and inflammatory response in SLE patients.O Lúpus Eritematoso Sistêmico (LES) é uma doença inflamatória autoimune multifatorial causada por perturbações do sistema imune, caracterizada pela quebra da autotolerância imune, ativação de linfócitos T autorreativos e hiperatividade de linfócitos B. Os nucleotídeos e o nucleosídeo da adenina, como o ATP e a adenosina, são componentes chave nos processos inflamatório e imune, inclusive modulando as funções dos linfócitos. Seus níveis extracelulares são regulados por ectoenzimas como a E-NTPDase que hidrolisa ATP/ADP até AMP; a enzima E-5’-nucleotidase que degrada AMP até adenosina e a E-adenosina desaminase (E-ADA) que converte a adenosina a inosina. O objetivo deste trabalho foi avaliar a atividade e expressão da E-NTPDase, a expressão da E-5’-nucleotidase e a atividade da E-ADA em linfócitos de pacientes com LES, bem como a atividade da ADA e a concentração de nucleotídeos e nucleosídeo no soro desses pacientes. Também tivemos como objetivo escrever um manuscrito de revisão sobre o tema após verificarmos lacunas na literatura em relação a sinalização purinérgica e LES. Foram selecionados 35 pacientes do Hospital Universitário de Santa Maria (HUSM) com diagnóstico de LES, o qual foi baseado em critérios de classificação do Systemic Lupus International Collaborating Clinics (SLICC) e 30 controles, dos quais amostras de sangue foram coletadas para a realização das análises. Os resultados mostraram um aumento da concentração de ATP no soro, possivelmente resultado do processo inflamatório, e uma redução dos níveis de adenosina nos pacientes com LES. Foi observada uma maior atividade (31%) e expressão (37%) da E-NTPDase em linfócitos de pacientes com LES. A atividade da E-ADA também encontrou-se aumentada, aproximadamente 42% nos linfócitos desses pacientes. Já a atividade da ADA no soro foi reduzida em 57%, em relação a expressão da E-5’-nucleotidase em linfócitos dos pacientes com LES não foram observadas diferenças. Analisamos também a atividade da E-NTPDase e ADA em dois grupos de pacientes, remissão e exacerbação, as quais não tiveram alterações possivelmente devido à presença constante de autoanticorpos e persistentes anormalidades mesmo durante a fase de remissão. O aumento evidenciado na atividade e expressão da E-NTPDase poderia representar um mecanismo para auxiliar no controle da inflamação, já que esta enzima exerce efeitos anti-inflamatórios através da remoção de ATP. Porém a atividade da E-ADA aumentada, nos linfócitos, poderia favorecer a resposta Th1 e limitar os efeitos anti-inflamatórios da adenosina. Por outro lado, a ADA no soro revelou-se diminuída o que poderia ser devido a prejudicada função dos macrófagos, apresentada por estes pacientes, já que a maior parte da ADA no soro tem como fonte essas células. Diante disto, concluímos que a E-NTPDase, a ADA e a via purinérgica possuem importante função na modulação da resposta imune e inflamatória nos pacientes com LES.porUniversidade Federal de Santa MariaCentro de Ciências Naturais e ExatasPrograma de Pós-Graduação em Ciências Biológicas: Bioquímica ToxicológicaUFSMBrasilBioquímicaAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessLúpus eritematoso sistêmicoATPAdenosinaE-NTPDaseADAE-5’-nucleotidaseSystemic lupus erythematosusAdenosineNTPDase5'-nucleotidaseCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICAPapel do sistema purinérgico no lúpus eritematoso sistêmico: um estudo clínico e de revisãoPurinergic system role in systemic lupus erythematosus: a clinical and review studyinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisSchetinger, Maria Rosa Chitolinahttp://lattes.cnpq.br/4401319386725357Prigol, Marinahttp://lattes.cnpq.br/6724052141066150Fachinetto, Roseleihttp://lattes.cnpq.br/7203076675431306Spanevello, Roselia Mariahttp://lattes.cnpq.br/3446031341157893Rech, Virginia Cielohttp://lattes.cnpq.br/0969715025616160http://lattes.cnpq.br/1160414675033184Becker, Lara Vargas200800000002600f2c5f39c-089e-4825-bfba-cc66b9098981bcdffe28-e6ed-41e1-bf64-bf0bbe95898b105a1dd4-1539-42e4-98da-9b7c360e25506a615e4f-285a-4d77-aeb6-a33cd9c07f80d4f3ac99-ac4b-4c34-b17a-4bba083d0e5a48cd3d46-c1ab-4d5f-8bd1-251331d88933reponame:Repositório Institucional Manancial UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALTES_PPGCB_2018_BECKER_LARA.pdfTES_PPGCB_2018_BECKER_LARA.pdfTese de Doutoradoapplication/pdf4524711http://repositorio.ufsm.br/bitstream/1/16489/1/TES_PPGCB_2018_BECKER_LARA.pdfe1f8b6768385360d8a26d1ce045a6408MD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; 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dc.title.por.fl_str_mv |
Papel do sistema purinérgico no lúpus eritematoso sistêmico: um estudo clínico e de revisão |
dc.title.alternative.eng.fl_str_mv |
Purinergic system role in systemic lupus erythematosus: a clinical and review study |
title |
Papel do sistema purinérgico no lúpus eritematoso sistêmico: um estudo clínico e de revisão |
spellingShingle |
Papel do sistema purinérgico no lúpus eritematoso sistêmico: um estudo clínico e de revisão Becker, Lara Vargas Lúpus eritematoso sistêmico ATP Adenosina E-NTPDase ADA E-5’-nucleotidase Systemic lupus erythematosus Adenosine NTPDase 5'-nucleotidase CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
title_short |
Papel do sistema purinérgico no lúpus eritematoso sistêmico: um estudo clínico e de revisão |
title_full |
Papel do sistema purinérgico no lúpus eritematoso sistêmico: um estudo clínico e de revisão |
title_fullStr |
Papel do sistema purinérgico no lúpus eritematoso sistêmico: um estudo clínico e de revisão |
title_full_unstemmed |
Papel do sistema purinérgico no lúpus eritematoso sistêmico: um estudo clínico e de revisão |
title_sort |
Papel do sistema purinérgico no lúpus eritematoso sistêmico: um estudo clínico e de revisão |
author |
Becker, Lara Vargas |
author_facet |
Becker, Lara Vargas |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Schetinger, Maria Rosa Chitolina |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/4401319386725357 |
dc.contributor.referee1.fl_str_mv |
Prigol, Marina |
dc.contributor.referee1Lattes.fl_str_mv |
http://lattes.cnpq.br/6724052141066150 |
dc.contributor.referee2.fl_str_mv |
Fachinetto, Roselei |
dc.contributor.referee2Lattes.fl_str_mv |
http://lattes.cnpq.br/7203076675431306 |
dc.contributor.referee3.fl_str_mv |
Spanevello, Roselia Maria |
dc.contributor.referee3Lattes.fl_str_mv |
http://lattes.cnpq.br/3446031341157893 |
dc.contributor.referee4.fl_str_mv |
Rech, Virginia Cielo |
dc.contributor.referee4Lattes.fl_str_mv |
http://lattes.cnpq.br/0969715025616160 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/1160414675033184 |
dc.contributor.author.fl_str_mv |
Becker, Lara Vargas |
contributor_str_mv |
Schetinger, Maria Rosa Chitolina Prigol, Marina Fachinetto, Roselei Spanevello, Roselia Maria Rech, Virginia Cielo |
dc.subject.por.fl_str_mv |
Lúpus eritematoso sistêmico ATP Adenosina E-NTPDase ADA E-5’-nucleotidase |
topic |
Lúpus eritematoso sistêmico ATP Adenosina E-NTPDase ADA E-5’-nucleotidase Systemic lupus erythematosus Adenosine NTPDase 5'-nucleotidase CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
dc.subject.eng.fl_str_mv |
Systemic lupus erythematosus Adenosine NTPDase 5'-nucleotidase |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
description |
Systemic Lupus Erythematosus (SLE) is a multifactorial inflammatory autoimmune disease caused by an immune dysfunction characterized by a breakdown of immune self-tolerance, activation of autoreactive T lymphocytes and B lymphocyte hyperactivity. The nucleotides and nucleoside adenine, such as ATP and adenosine, are key components in inflammatory and immune processes, including the modulation of lymphocyte functions. Their extracellular levels are regulated by ectoenzymes such as E-NTPDase which hydrolyzes ATP / ADP to AMP; E-5'-nucleotidase that degrades AMP to adenosine and E-adenosine deaminase (E-ADA) that converts adenosine to inosine. In this work, we determined the activity and expression of E-NTPDase, E-5'-nucleotidase expression, and E-ADA activity in lymphocytes, as well as ADA activity and nucleotide and nucleoside concentration in the serum of SLE patients. We also aimed to fill in some gaps we observed in the literature by writing a review article regarding purinergic signaling and SLE. Thirty-five patients from the University Hospital of Santa Maria (HUSM) with a diagnosis of SLE were selected, based on the Systemic Lupus International Collaborating Clinics (SLICC) classification criteria and 30 controls, from which blood samples were collected for the analyzes. The results showed an increase in the serum ATP concentration, possibly as a result of inflammation, and a decrease in adenosine levels in SLE patients. Increased activity (31%) and expression (37%) of E-NTPDase were observed in lymphocytes of SLE patients. The activity of E-ADA was also increased by approximately 42% in the lymphocytes of these patients. The serum ADA activity was reduced by 57%. Regarding the expression of E-5'-nucleotidase in lymphocytes of patients with SLE, no differences were observed. The increase observed in the activity and expression of E-NTPDase could represent a mechanism to help in the control of inflammation, since this enzyme exerts anti-inflammatory effects through the removal of ATP. However, increased E-ADA activity in lymphocytes could favor a Th1 response and limit the anti-inflammatory effects of adenosine. On the other hand, serum ADA has been shown to be decreased due to the impaired macrophage function present in these patients since most of the serum ADA comes from these cells. When we checked a gap in the literature regarding purinergic signaling and SLE, we decided to write a review on the topic to elucidate the effects of ATP and E-NTPDase on SLE and contribute to the understanding of SLE in this context. In view of this, we conclude that the NTPDase, ADA and the purinergic pathway play an important role in modulating the immune and inflammatory response in SLE patients. |
publishDate |
2018 |
dc.date.issued.fl_str_mv |
2018-12-18 |
dc.date.accessioned.fl_str_mv |
2019-05-08T19:24:19Z |
dc.date.available.fl_str_mv |
2019-05-08T19:24:19Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/16489 |
url |
http://repositorio.ufsm.br/handle/1/16489 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.cnpq.fl_str_mv |
200800000002 |
dc.relation.confidence.fl_str_mv |
600 |
dc.relation.authority.fl_str_mv |
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dc.rights.driver.fl_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências Naturais e Exatas |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica |
dc.publisher.initials.fl_str_mv |
UFSM |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Bioquímica |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências Naturais e Exatas |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional Manancial UFSM instname:Universidade Federal de Santa Maria (UFSM) instacron:UFSM |
instname_str |
Universidade Federal de Santa Maria (UFSM) |
instacron_str |
UFSM |
institution |
UFSM |
reponame_str |
Repositório Institucional Manancial UFSM |
collection |
Repositório Institucional Manancial UFSM |
bitstream.url.fl_str_mv |
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bitstream.checksum.fl_str_mv |
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bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 MD5 MD5 |
repository.name.fl_str_mv |
Repositório Institucional Manancial UFSM - Universidade Federal de Santa Maria (UFSM) |
repository.mail.fl_str_mv |
ouvidoria@ufsm.br |
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1808854728339095552 |