inalização via Akt1 em células dendríticas modula a interação microbiota-hospedeiro e a reabsorção óssea inflamatória
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Data
2018-03-26
Autores
Cabrera Ortega, Adriana Alicia
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Universidade Estadual Paulista (Unesp)
Resumo
Células dendríticas têm papel crucial na patogênese das doenças periodontais por orquestrarem a resposta imune adaptativa e por seu papel como precursoras de osteoclastos. A sinalização via Akt tem importante papel em processos como metabolismo, proliferação, apoptose e também na resposta imune. Evidências indicam que Akt1 tem papel de regulador endógeno negativo da resposta inflamatória; porém pode tanto estimular quanto inibir a osteoclastogênese. Considerando que as células dendríticas participam tanto da inflamação/resposta imune quanto do turnover do tecido ósseo como células precursoras de osteoclastos, propusemos avaliar através de um estudo in vivo o papel da atividade de Akt1 na inflamação associada a interações microbiota-hospedeiro, bem como investigar in vitro os efeitos desta via de sinalização sobre os diferentes eventos biológicos das células dendríticas. Para o estudo in vivo foi utilizado um modelo de doença periodontal experimental induzida por P. gingivalis e Fusobacterium nucleatum, em um modelo de animais transgênicos com deleção gênica condicional. Os desfechos avaliados foram: inflamação (morfometria), reabsorção óssea (μCT), osteoclastogênese (IHC), anticorpos específicos para P.gingivalis e Fusobacterium nucleatum (ELISA). No estudo in vitro foi avaliado o papel da via de sinalização Akt1 sobre as seguintes atividades das células dendríticas: proliferação, apoptose, atividade fagocitária, migração, apresentação de antígeno e osteoclastogênese. Resultados do estudo in vivo demonstraram que a sinalização via Akt1 em células dendríticas parece ter um papel importante na patogênese da doença periodontal, podendo modificar a intensidade da resposta imune adaptativa assim como sua diferenciação osteoclástica, modificando assim o turnover fisiológico do osso alveolar. Adicionalmente, é possível concluir que a sinalização via Akt é necessária para o desenvolvimento das funções biológicas (proliferação, fagocitose, apresentação de antígeno e diferenciação osteoclástica) das células dendríticas.
Dendritic cells play a crucial role in the pathogenesis of periodontal diseases by orchestrating the adaptive immune response and their role as osteoclasts precursors. Akt signaling plays an important role in processes such as metabolism, proliferation, apoptosis and also in the immune response. Evidence indicates that Akt1 plays a role of negative endogenous regulator of the inflammatory response; but can both stimulate and inhibit osteoclastogenesis. Considering that dendritic cells participate in both inflammation/immune response and turnover of bone tissue as osteoclast precursor cells, we have proposed to evaluate in a vivo study the role of Akt1 activity in inflammation associated with microbiota-host interactions, as well as to evaluate in vitro the role of the Akt1 signaling pathway in dendritic cell biology. In vivo study was employed a model of experimental periodontal disease induced by P. gingivalis and Fusobacterium nucleatum in transgenic animals model with conditional gene deletion. The outcomes evaluated were: inflammation (morphometry), bone resorption (μCT), osteoclastogenesis (IHC), antibodies specific for P.gingivalis and Fusobacterium nucleatum (ELISA). In vitro study was evaluated the role of Akt1 signaling pathway on the following outcomes related to dendritic cell biology: proliferation, apoptosis, phagocytic activity, migration, antigen presentation and osteoclastogenesis The results showed that signaling via Akt1 in dendritic cells seems to play an important role in the pathogenesis of periodontal disease, modifying the intensity of the adaptive immune response as well as its capacity in osteoclastic differentiation, thus modifying the physiological turnover of the alveolar bone. Futhermore, it is possible to conclude that Akt signaling is necessary for the development of biological functions (proliferation, phagocytosis, antigen presentation and osteoclast differentiation) of dendritic cells.
Dendritic cells play a crucial role in the pathogenesis of periodontal diseases by orchestrating the adaptive immune response and their role as osteoclasts precursors. Akt signaling plays an important role in processes such as metabolism, proliferation, apoptosis and also in the immune response. Evidence indicates that Akt1 plays a role of negative endogenous regulator of the inflammatory response; but can both stimulate and inhibit osteoclastogenesis. Considering that dendritic cells participate in both inflammation/immune response and turnover of bone tissue as osteoclast precursor cells, we have proposed to evaluate in a vivo study the role of Akt1 activity in inflammation associated with microbiota-host interactions, as well as to evaluate in vitro the role of the Akt1 signaling pathway in dendritic cell biology. In vivo study was employed a model of experimental periodontal disease induced by P. gingivalis and Fusobacterium nucleatum in transgenic animals model with conditional gene deletion. The outcomes evaluated were: inflammation (morphometry), bone resorption (μCT), osteoclastogenesis (IHC), antibodies specific for P.gingivalis and Fusobacterium nucleatum (ELISA). In vitro study was evaluated the role of Akt1 signaling pathway on the following outcomes related to dendritic cell biology: proliferation, apoptosis, phagocytic activity, migration, antigen presentation and osteoclastogenesis The results showed that signaling via Akt1 in dendritic cells seems to play an important role in the pathogenesis of periodontal disease, modifying the intensity of the adaptive immune response as well as its capacity in osteoclastic differentiation, thus modifying the physiological turnover of the alveolar bone. Futhermore, it is possible to conclude that Akt signaling is necessary for the development of biological functions (proliferation, phagocytosis, antigen presentation and osteoclast differentiation) of dendritic cells.
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Palavras-chave
Doenças periodontais, Células dendríticas, Proteínas proto-oncogênicas c-Akt, Imunidade inata, Imunidade adaptativa, Periodontal diseases, Dendritic cells, Proto-oncogene proteins c-Akt, Innate immunity, Adaptive immunity