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[PMID]: | 28807491 |
[Au] Autor: | Ahmad SF; Ansari MA; Nadeem A; Bakheet SA; Almutairi MM; Attia SM |
[Ad] Endereço: | Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Electronic address: fashaikh@ksu.edu.sa. |
[Ti] Título: | Adenosine A2A receptor signaling affects IL-21/IL-22 cytokines and GATA3/T-bet transcription factor expression in CD4 T cells from a BTBR T Itpr3tf/J mouse model of autism. |
[So] Source: | J Neuroimmunol;311:59-67, 2017 Oct 15. | [Is] ISSN: | 1872-8421 |
[Cp] País de publicação: | Netherlands |
[La] Idioma: | eng |
[Ab] Resumo: | Autism is a complex heterogeneous neurodevelopmental disorder; previous studies have identified altered immune responses among individuals diagnosed with autism. An imbalance in the production of pro- and anti-inflammatory cytokines and transcription factors plays a role in neurodevelopmental behavioral and autism disorders. BTBR T Itpr3tf/J (BTBR) mice are used as a model for autism, as they exhibit social deficits, communication deficits, and repetitive behaviors compared with C57BL/6J (B6) mice. The adenosine A2A receptor (A2AR) appears to be a potential target for the improvement of behavioral, inflammatory, immune, and neurological disorders. We investigated the effects of the A2AR antagonist SCH 5826 (SCH) and agonist CGS 21680 (CGS) on IL-21, IL-22, T-bet, T-box transcription factor (T-bet), GATA3 (GATA Binding Protein 3), and CD152 (CTLA-4) expression in BTBR mice. Our results showed that BTBR mice treated with SCH had increased CD4 IL-21 , CD4 IL-22 , CD4 GATA3 , and CD4 T-bet and decreased CD4 CTLA-4 expression in spleen cells compared with BTBR control mice. Moreover, CGS efficiently decreased CD4 IL-21 , CD4 IL-22 , CD4 GATA3 , and CD4 T-bet and increased CD4 CTLA-4 production in spleen cells compared with SCH-treated and BTBR control mice. Additionally, SCH treatment significantly increased the mRNA and protein expression levels of IL-21, IL-22, GATA3, and T-bet in brain tissue compared with CGS-treated and BTBR control mice. The augmented levels of IL-21/IL-22 and GATA3/T-bet could be due to altered A2AR signaling. Our results indicate that A2AR agonists may represent a new class of compounds that can be developed for use in the treatment of autistic and neuroimmune dysfunctions. |
[Mh] Termos MeSH primário: |
Transtorno Autístico/patologia Linfócitos T CD4-Positivos/metabolismo Citocinas/metabolismo Fator de Transcrição GATA3/metabolismo Receptor A2A de Adenosina/metabolismo Transdução de Sinais/genética
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[Mh] Termos MeSH secundário: |
Adenosina/análogos & derivados Adenosina/farmacologia Agonistas do Receptor A2 de Adenosina/farmacologia Antagonistas do Receptor A2 de Adenosina/farmacologia Animais Transtorno Autístico/genética Transtorno Autístico/imunologia Encéfalo/metabolismo Linfócitos T CD4-Positivos/efeitos dos fármacos Modelos Animais de Doenças Proteínas Fetais/genética Proteínas Fetais/metabolismo Regulação da Expressão Gênica/efeitos dos fármacos Regulação da Expressão Gênica/genética Receptores de Inositol 1,4,5-Trifosfato/genética Masculino Camundongos Camundongos Endogâmicos C57BL Camundongos Mutantes Neurológicos Proteínas do Tecido Nervoso/deficiência Proteínas do Tecido Nervoso/genética Fenetilaminas/farmacologia Pirimidinas/farmacologia Transdução de Sinais/efeitos dos fármacos Baço/patologia Proteínas com Domínio T-Box/genética Proteínas com Domínio T-Box/metabolismo Triazóis/farmacologia
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[Pt] Tipo de publicação: | JOURNAL ARTICLE |
[Nm] Nome de substância:
| 0 (5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine); 0 (Adenosine A2 Receptor Agonists); 0 (Adenosine A2 Receptor Antagonists); 0 (Brachyury protein); 0 (Cytokines); 0 (Disc1 protein, mouse); 0 (Fetal Proteins); 0 (GATA3 Transcription Factor); 0 (ITPR3 protein, mouse); 0 (Inositol 1,4,5-Trisphosphate Receptors); 0 (Nerve Tissue Proteins); 0 (Phenethylamines); 0 (Pyrimidines); 0 (Receptor, Adenosine A2A); 0 (T-Box Domain Proteins); 0 (Triazoles); 120225-54-9 (2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine); K72T3FS567 (Adenosine) |
[Em] Mês de entrada: | 1709 |
[Cu] Atualização por classe: | 170926 |
[Lr] Data última revisão:
| 170926 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 170816 |
[St] Status: | MEDLINE |
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