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Master's Dissertation
DOI
10.11606/D.87.2010.tde-01122010-110647
Document
Author
Full name
Luiz Antonio Gerardi Junior
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2010
Supervisor
Committee
Borges, Monamaris Marques (President)
Barbosa, Ângela Silva
Gomes, Ligia Ferreira
Title in Portuguese
Avaliação da atividade imunomoduladora da microplusina sobre macrófagos murinos in vitro.
Keywords in Portuguese
Adjuvantes imunológicos
Citocinas
Imunomoduladores
Inflamação
Macrófagos
Óxido nítrico
Peptídeos
Abstract in Portuguese
Peptídeos de defesa do hospedeiro antimicrobiano (PDHA) são componentes do sistema imune inato podem ser expressos constitutivamente ou induzidos por componentes bacterianos, citocinas, ou a combinação de ambos. Estes peptídeos possuem ação direta sobre microrganismo e são potentes imunomoduladores de células de mamíferos. A microplusina é um peptídeo antimicrobiano quelante de cobre, originário do aracnídeo Tick Rhipicephalus (Boophilus) microplus, com massa molecular de 10 204 Da. Este peptídeo possue atividade bacteriostática sobre Micrococcus luteus, mas sem atividade microbicida sobre E. coli e Candida albicans. Neste trabalho foi analisado o efeito direto da microplusina em cultura de macrófagos derivados de medula óssea (MDM) tratados ou não com LPS ou IFN-γ. Foi demonstrado que este peptídeo não teve efeito citotóxico para macrófagos, não estimulou a síntese de NO e IL-1β, mas aumentou a produção de TNF-α e IL-6 após estímulo. O pré-tratamento dos macrófagos com microplusina, antes da adição do LPS, não modificou o nível de nitrito, TNF-α ou IL-6 em resposta ao LPS. Quando os macrófagos foram pré-tratados com microplusina e posteriormente incubados com IFN-γ houve aumento significativo da produção de NO e TNF-α, confirmando a natureza pró-inflamatória deste peptídeo. Isto indica que a microplusina é um agente imunomodulador da resposta imune inata e pode auxiliar no controle de infecções por microrganismos patogênicos.
Title in English
Evaluation of immunomodulatory activity of microplusin in murine macrophage in vitro.
Keywords in English
Cytokines
Immunological adjuvants
Immunomodulators
Inflammation
Macrophages
Nitric oxide
Peptides
Abstract in English
Antimicrobial host defense peptides are components of the innate immune system. They are expressed constitutively or induced by bacterial components, cytokines or the combination of both are expressed constitutively or induced by bacterial components, cytokines, or a combination of both. These peptides have direct action on microorganisms and are potent immunomodulators in mammalian cells. Microplusin is a copper II-chelating antimicrobial peptide from the Tick Rhipicephalus ( Boophilus) microplus, with a molecular mass of 10 204 Da. This peptide has a bacteriostatic activity against Micrococcus luteus, but no activity against E. coli and Candida albicans. The aim of the present work was to analyze the direct effect of microplusin in the culture of murine bone marrow derivated macrophages (BDM) treated or not with LPS or IFN-γ. Our data showed that microplusin had no cytotoxic effect on macrophages, did not stimulate the synthesis of NO and IL-1β, but increased the production of TNF-α and IL-6 after stimulation. The pre-treatment of macrophages with microplusin before LPS addition did not change the level of nitrite, TNF-α or IL-6 in response to LPS. If the microplusin pre-treated macrophages were incubated with IFN-γ there was evidence that microplusin led to significant increase of NO and TNF-α production confirming the pro-inflammatory characteristic of microplusin and its potential against pathogenic microorganisms. This indicates microplusin to be a potential immunomodulating agent of innate immunity and may help to control infections by pathogenic microorganisms.
 
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Publishing Date
2010-12-01
 
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