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Master's Dissertation
DOI
https://doi.org/10.11606/D.87.2013.tde-06112013-100747
Document
Author
Full name
Rafael Salim Nassar
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2013
Supervisor
Committee
Borges, Monamaris Marques (President)
Gomes, Ligia Ferreira
Mendonça, Ronaldo Zucatelli
Title in Portuguese
Potencial da migalina (Acilpoliamina) como agente imunomodulador das funções de macrófagos murinos.
Keywords in Portuguese
Adjuvantes imunológicos
Camundongos
Citocinas
Fagocitose
Abstract in Portuguese
As poliaminas são essenciais para o controle dos mecanismos celulares nos seres vivos. A Migalina é uma acilpoliamina isolada de A. gomesiana com atividade microbicida contra E. coli, contudo, seu efeito imunomodulador é desconhecido. Sabendo que os mediadores imunes produzidos por macrófagos são críticos para a regulação da resposta imune, investigamos o efeito in vitro da Migalina sobre estas células. Demonstramos que a Migalina não induziu citotoxicidade, mas ativou iNOS, potencializando a síntese de nitrito. Aumentou a produção de TNF-a, mas não de IL-12p40. IL-1b não foi detectada. Além disto, Inibiu a produção de TNF-a e IL-12p40 induzida por LPS e quando associada à Polimixina B não alterou a síntese de TNF-a. Macrófagos deficientes de MyD88 não produziram TNF-a em resposta a Migalina, sugerindo que a sinalização mediada por TLR via MyD88 é requerida para a produção desta citocina. Comprovamos que a Migalina modula a atividade de macrófagos através de mediadores da resposta imune inata e pode ser explorada como estratégia no controle de infecções.
Title in English
The potential of Mygalin (Acylpolyamine) as an immunomodulator agent of murine macrophage functions.
Keywords in English
Cytokines
Immune adjuvants
Mice
Phagocytosis
Abstract in English
Polyamines are present in most living organisms. Mygalin is an acylpolyamine isolated from A. gomesiana that showed microbicide activity against E. coli, however, its immunomodulator effect has not been explored. Immune mediators produced by macrophages are essential for the regulation of immune responses. Our results showed that murine macrophages stimulated in vitro with Mygalin didnt induce cytotoxicity, but activated iNOS, inducing nitrite synthesis. The production of TNF-a was enhanced, but IL-12p40 was not. The presence of IL-1b was not detected. In higher concentrations, Mygalin inhibited significantly the production of IL-12p40 and TNF-a induced by LPS, and its association with Polymixine B did not altered the production profile of TNF-a. Macrophages deficient in MyD88 molecule activated with Mygalin did not induce the synthesis of TNF-a. Our results showed that Mygalin is capable of modulating the macrophage activity by inducing mediators of innate immune response and can be explored as a strategy in the studies to control pathogen infections.
 
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Publishing Date
2014-01-16
 
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