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Master's Dissertation
DOI
10.11606/D.99.2017.tde-18052017-113408
Document
Author
Full name
Ariane Farias Leal
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2017
Supervisor
Committee
Goto, Hiro (President)
Gomes, Claudia Maria de Castro
Starobinas, Nancy
Title in Portuguese
Influência do fator de crescimento insulina-símile ("insulin-like growth factor" = IGF-I) no parasitismo de macrófagos peritoneais de camundongos por Leishmania (L.) infantum
Keywords in Portuguese
Expressão gênica
Fator de crescimento insulin-like I
Leishmania infantum
Óxido nítrico
Parasitismo
RNA
Abstract in Portuguese
Nas leishmanioses, sabe-se que tanto na resistência quanto na suscetibilidade à infecção, a resposta imune celular é considerada a mais importante. No entanto, na fase inicial, fatores inespecíficos estão sendo considerados fundamentais na determinação do curso da doença, como o fator de crescimento insulina-símile I ("insulin-like growth factor"-IGF-I). Em trabalhos anteriores realizados no grupo de pesquisa da Profa. Dra. Hiro Goto mostraram que IGF-I extrínseco favorece a proliferação do parasito e progressão da infecção, com diminuição na produção de óxido nítrico e ativação da arginase de macrófagos e do parasito. Sabendo que os macrófagos produzem intrinsecamente IGF-I, avaliamos o efeito do fator intrínseco no parasitismo em macrófagos de camundongos BALB/c infectados por L. (L.) infantum silenciando a expressão do RNA mensageiro (mRNA) de IGF-I na célula pela técnica de RNA de interferência (siRNA). Iniciamos avaliando a expressão do mRNA de IGF-I e do seu receptor (IGF-IR). Foi observado uma diminuição de 1,4 vezes da expressão do mRNA de IGF-I em 24 horas e um aumento de 1,5 vezes em 48 horas quando comparado com o grupo controle. Também foi observado um aumento na expressão de mRNA do receptor de IGF-I em 24 como em 48 horas nos grupos infectados quando comparado com o grupo controle. Com o silenciamento do IGF-I por siRNA, houve diminuição da expressão de mRNA do IGF-I no macrófago em torno de 71% em 24 horas e de 51% em 48 hora. Na ausência ou diminuição do IGF-I no macrófago, observou-se uma diminuição do parasitismo na infecção com promastigotas, sendo o parasitismo recuperado com a reposição de IGF-I extrínseco no sistema, atestando a importância de IGF-I na proliferação do parasito. Esses resultados reforçam a importância do IGF-I na infecção por L. infantum, sugerindo que o IGF-I está diretamente relacionado ao parasitismo.
Title in English
Influence of Insulin-like growth factor (IGF) -I on the parasitism of mice peritoneal macrophages by Leishmania (L.) infantum
Keywords in English
Gene expression
Insulin-like growth factor I
Leishmania infantum
Nitric oxide
Parasitism
RNA
Abstract in English
In leishmaniasis, it is known that in both resistance and susceptibility to infection, the cellular immune response is considered the most important. However, in the initial phase, nonspecific factors are being considered as fundamental in determining the course of the disease, such as insulin-like growth factor I (IGF-I). Studies carried out in the research group of Profa. Dr. Hiro Goto showed that extrinsic IGF-I favors parasite proliferation and infection progression, with decrease in nitric oxide production and activation of arginase of macrophages and parasite. It is known that macrophages produced IGF-I (intrinsic IGF-I), thus, in the present study we have investigated the effect of the intrinsic factor in the parasitism on macrophages of BALB/c mice infected with L. (L.) infantum by silencing the expression of messenger RNA (IGF-I mRNA) in the cell by the interference RNA technique (siRNA). We started evaluating the expression of IGF-I mRNA and its receptor (IGF-IR). A 1.4-fold decrease in IGF-I mRNA expression was observed in 24 hours and a 1.5-fold increase in 48 hours as compared to the control group. An increase in mRNA expression of the IGF-IR was also observed in 24 as well as in 48 hours in the infected groups as compared to the control group. With IGF-I silencing by siRNA, there was a decrease in IGF-I mRNA expression in the macrophage around 71% in 24 hours and 51% in 48 hours. In the absence or decrease of IGF-I in the macrophage, a decrease in the parasitism in the infection with promastigotes was observed, and the parasitism recovered with the replacement of extrinsic IGF-I in the system, confirming the importance of IGF-I in the proliferation of the parasite. These results reinforce the importance of IGF-I in L. infantum infection, suggesting that IGF-I is directly related to the parasitism.
 
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Release Date
2019-05-18
Publishing Date
2017-05-18
 
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