Elevada concentração de glicose altera a resposta biológica de linhagem de células dendríticas murina
Carregando...
Data
2016-07-21
Autores
Souza, Sabrina Cruz Tfaile Frasnelli de [UNESP]
Título da Revista
ISSN da Revista
Título de Volume
Editor
Universidade Estadual Paulista (Unesp)
Resumo
Diabetes mellitus (DM) é uma desordem metabólica importante caracterizada pela ausência de secreção e/ou ação deficiente da insulina, resultando em hiperglicemia crônica e persistente que é a principal característica do DM. A influência do diabetes sobre as doenças periodontais é amplamente documentada e reconhecida demonstrando que a desregulação da resposta imune associada ao diabetes afeta a interação microbiota-hospedeiro no periodonto, aumentando a severidade e extensão da destruição dos tecidos periodontais. Considerando o papel crucial das células dendríticas (DC) no desenvolvimento e regulação da resposta imune e da relativa escassez de informação sobre a influência específica de concentrações elevadas de glicose nas células imunes, investigou-se a hipótese de que a elevada glicose influencia a biologia de DCs. Especificamente, avaliamos a influência da alta de glicose sobre a proliferação e viabilidade, a apoptose, a maturação, a quimiotaxia, a migração para os linfonodos (homing), atividade fagocitária, expressão de mediadores inflamatórios e produção de espécies reativas de oxigénio (ROS). Foram utilizadas células dendríticas de linhagem murina (DC2.4), que foram expostas a concentração elevada (25 mM) ou normal (11,1 mM) de glicose, por períodos que variaram de 24 a 72 h. A exposição à alta glicose reduziu a proliferação mas não afetou a viabilidade, a sobrevivência ou a maturação de células DC2.4 induzida por LPS; no entanto a susceptibilidade à apoptose foi aumentada. Alta de glicose também reduziu atividade fagocitária, a quimiotaxia e o homing para os gânglios linfáticos in vivo. Por outro lado, a produção de ROS e expressão gênica de mediadores inflamatórios foram aumentadas em elevadas concentrações de glicose. Coletivamente, os efeitos da alta glicose na biologia de células dendríticas são consistentes e mostram uma diminuição na função de ativação imune de DCs e uma exacerbação da inflamação local.
Diabetes mellitus (DM) is a major metabolic disorder characterized by the absence of secretion and/or impaired insulin action, resulting in chronic and persistent hyperglycemia which is the main characteristic of DM. The effect of diabetes on periodontal diseases is widely recognized and documented demonstrating that dysregulation of the immune response associated with diabetes affects microbial-host interaction in the periodontium, increasing the severity and extent of the destruction of the periodontal tissues. Considering the crucial role of dendritic cells (DCs) in the development and regulation of immune response and the relative scarcity of information on the specific influence of high glucose concentrations on immune cells, we investigated the hypothesis that high glucose influences the biology of DCs. Specifically, we assessed the influence of high glucose on proliferation and viability, apoptosis, maturation, chemotaxis, migration to the lymph nodes (homing), phagocytic activity, expression of inflammatory mediators and production of reactive oxygen species (ROS). We used a murine dendritic cell line (DC2.4), which was exposed to high (25 mM) or normal (11.1 mM) glucose concentrations for periods ranging from 24 to 72 h. Exposure to high glucose reduced proliferation but did not affect viability, survival or LPS-induced maturation of DC2.4 cells; however susceptibility to apoptosis was increased. High glucose also reduced phagocytic activity, chemotaxis and homing to lymph nodes in vivo. On the other hand, production of ROS and gene expression of inflammatory mediators were increased by high glucose. Collectively, the effects of high glucose on dendritic cell biology are consistent with a decrease on immune activating role of DCs and an exacerbation of local inflammation.
Diabetes mellitus (DM) is a major metabolic disorder characterized by the absence of secretion and/or impaired insulin action, resulting in chronic and persistent hyperglycemia which is the main characteristic of DM. The effect of diabetes on periodontal diseases is widely recognized and documented demonstrating that dysregulation of the immune response associated with diabetes affects microbial-host interaction in the periodontium, increasing the severity and extent of the destruction of the periodontal tissues. Considering the crucial role of dendritic cells (DCs) in the development and regulation of immune response and the relative scarcity of information on the specific influence of high glucose concentrations on immune cells, we investigated the hypothesis that high glucose influences the biology of DCs. Specifically, we assessed the influence of high glucose on proliferation and viability, apoptosis, maturation, chemotaxis, migration to the lymph nodes (homing), phagocytic activity, expression of inflammatory mediators and production of reactive oxygen species (ROS). We used a murine dendritic cell line (DC2.4), which was exposed to high (25 mM) or normal (11.1 mM) glucose concentrations for periods ranging from 24 to 72 h. Exposure to high glucose reduced proliferation but did not affect viability, survival or LPS-induced maturation of DC2.4 cells; however susceptibility to apoptosis was increased. High glucose also reduced phagocytic activity, chemotaxis and homing to lymph nodes in vivo. On the other hand, production of ROS and gene expression of inflammatory mediators were increased by high glucose. Collectively, the effects of high glucose on dendritic cell biology are consistent with a decrease on immune activating role of DCs and an exacerbation of local inflammation.
Descrição
Palavras-chave
Diabetes mellitus, Células dendríticas, Inflamação, Dendritic cell, Inflammation