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| Author(s): |
Fernanda Narangeira de Araújo
Total Authors: 1
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| Document type: | Master's Dissertation |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Instituto de Medicina Tropical de São Paulo (IMT) |
| Defense date: | 2019-11-27 |
| Examining board members: |
Hiro Goto;
Cyro Alves de Brito;
Luciana Regina Meireles Jaguaribe Ekman
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| Advisor: | Hiro Goto |
| Abstract | |
Th1 and Th2 profile-defining cytokines influence the evolution of leishmaniasis infection and also the expression of insulin-like growth factor I (IGF-I) in macrophages. Our group has previously shown that IGF-I is an effector factor of cytokine IL-4 during Leishmania major infection. However, as the response may differ depending on the species of Leishmania, we propose to analyze the effects of cytokines IL-4, IL-13 and IFN-? on the expression of IGF-I and its receptor and its correlation with parasitism in the infection of RAW cells with Leishmania (Leishmania) amazonensis. The macrophage lineage RAW 264.7 (5x105 cells) was infected with L. (L.) amazonensis promastigotes and treated with IL-4, IL-13 and IFN- ? for 24, 48 and 72 hours. We evaluated the expression of Igf-I mRNA and its receptor by RealTime PCR relative quantification, parasitism, nitric oxide production and arginase activity. Regarding Th2 cytokines, IL-4 and IL-13, an increase in parasitism associated with increased IGF-I expression and increased arginase activity was observed. After stimulation with cytokine IFN-?, observe a increase parasitism, increase nitric oxide production and decrease IGF-I expression. In the IGF-I receptor evaluation, we observed a decrease in Igf-IR mRNA expression in all discount groups. IGF-I silencing by interfering RNA (siRNA) resulted in decreased mRNA expression (> 90%). Regarding the parasitism of these cells, we observed a significant decrease in parasitism in the siRNA groups when compared to the control without siRNA at 24 and 48 hours. In assessing the participation of Th1 and Th2 cytokines in parasitism after IGF-I silencing, all siRNA-treated and cytokine-stimulated groups showed decreased parasitism relative to their controls without siRNA. In L. amazonensis infection, the Th1 profile cytokine, IFN-?, has a different effect on parasitism when compared to L. major infection. Our results suggest that IGF-I has a direct effect on parasitism and that even with cytokine stimuli, the presence of IGF-I is necessary to promote susceptibility of infection. (AU) | |
| FAPESP's process: | 17/02959-4 - Interaction of Insulin-Like Growth Factor I and cytokines Th1 and Th2 in murine macrophage infection by Leishmania (Leishmania) amazonensis |
| Grantee: | Fernanda Narangeira de Araujo |
| Support Opportunities: | Scholarships in Brazil - Master |