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Doctoral Thesis
DOI
10.11606/T.42.2010.tde-10012011-152253
Document
Author
Full name
Marco Aurelio Ramirez Vinolo
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2010
Supervisor
Committee
Curi, Rui (President)
Abdulkader, Fernando Rodrigues de Moraes
Câmara, Niels Olsen Saraiva
Garcia, Primavera Borelli
Soriano, Francisco Garcia
Title in Portuguese
Efeito dos ácidos graxos de cadeia curta sobre neutrófilos.
Keywords in Portuguese
Candida albicans
Ácidos graxos de cadeia longa
Citocinas
Fagocitose
Inflamação
Neutrófilos
Peroxidase
Abstract in Portuguese
Neste estudo avaliamos o efeito dos AGCC (acetato, propionato e butirato) sobre o recrutamento de neutrófilos e parâmetros funcionais (espécies reativas de oxigênio [ERO], citocinas e óxido nítrico, fagocitose e destruição de C. albicans). Investigamos ainda a ativação do NFkB, efeito sobre histonas desacetilases (HDAC) e GPR43. Acetato e butirato alteraram a produção de ERO; o primeiro aumentou a produção de peróxido de hidrogênio, enquanto o butirato inibiu a produção estimulada por PMA. O butirato reduziu a fagocitose e killing de leveduras. Propionato e butirato reduziram a produção de TNF-α, CINC-2αb e óxido nítrico e aumentaram a síntese de IL-1β por neutrófilos estimulados com LPS. Esses efeitos decorreram de ação a nível transcricional e devem envolver inibição da atividade de HDAC e da ativação do NFkB. Os AGCC aumentaram a migração de neutrófilos in vitro e in vivo. Esses efeitos decorreram de aumento da produção de CINC-2αb pelo tecido e da ação direta dos AGCC via GPR43. Os AGCC apresentam ações pró- e antiinflamatórias dependendo do parâmetro analisado.
Title in English
Effect of short chain fatty acids on neutrophils function.
Keywords in English
Candida albicans
Cytokines
Inflammation
Neutrophils
Peroxidase
Phagocytosis
Snort-chain fatty acids
Abstract in English
We evaluated the effect of SCFA (acetate, propionate and butyrate) on the recruitment of neutrophils and functional parameters (reactive oxygen species [ROS], cytokines and nitric oxide production, phagocytosis and destruction of C. albicans). We also investigated the activation of NFkB, effect on histone deacetylases (HDAC) and GPR43. Acetate and butyrate altered the production of ROS, the former increased the production of hydrogen peroxide, whereas butyrate inhibited the production stimulated by PMA. Butyrate reduced the phagocytosis and killing of yeast. Propionate and butyrate reduced the production of TNF-α, CINC-2αb and nitric oxide and increased the synthesis of IL-1β by LPS-stimulated neutrophils. These effects involve modification at the transcriptional level and inhibition of HDAC and NFkB activation. SCFA increased neutrophil migration in vitro and in vivo, an effect that may be the result of increased production of CINC-2αb and direct action of GPR43. SCFA present pro- and anti-inflammatory actions depending on the parameter analyzed.
 
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Publishing Date
2011-05-05
 
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