Insulin-Like Growth Factor-I as an Effector Element of the Cytokine IL-4 in the Development of a Leishmania major Infection

Autor(es)

Reis, Luiza C. ; Ramos-Sanchez, Eduardo Milton ; Petitto-Assis, Fabricio ; Nerland, Audun H. ; Hernandez-Valladares, Maria ; Selheim, Frode ; Floeter-Winter, Lucile Maria ; Goto, Hiro

• Tipo de documento: Artigo Científico
• Fonte: Mediators of Inflammation; v. 2018, p. 17-pg., 2018-01-01.

Resumo

Certain cytokines modulate the expression of insulin-like growth factor-(IGF-) I. Since IL-4 and IGF-I promote growth of the protozoan Leishmania major, we here addressed their interaction in downregulating the expression of Igf-I mRNA using small interfering RNA (siRNA) in Leishmania major-infected macrophages. Parasitism was decreased in the siRNA-treated cells compared with the nontreated cells, reversed by the addition of recombinant IGF-I (rIGF-I). In IL-4-stimulated macrophages, parasitism and the Igf-I mRNA amount were increased, and the effects were nullified upon siRNA transfection. IGF-I downregulation inhibited both parasite and macrophage arginase activation even in IL-4-stimulated cells. Searching for intracellular signaling components shared by IL-4 and IGF-I, upon siRNA transfection, phosphorylated p44, p38, and Akt proteins were decreased, affecting the phosphatidylinositol-3-kinase (PI3K)/Akt pathway. In L. major-infected C57BL6-resistant mice, the preincubation of the parasite with rIGF-I changed the infection profile to be similar to that of susceptible mice. We conclude that IGF-I constitutes an effector element of IL-4 involving the PI3K/Akt pathway during L. major infection. (AU)

• Processo FAPESP: 05/52271-1 - Participacao do fator de crescimento insulina-simile (igf-i) na imunidade especifica a infeccao por leishimania (l.) major.
• Beneficiário: Fabricio Petitto de Assis
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 08/04106-0 - O papel do fator de crescimento insulina-símile I (IGF-I) na modulação do efeito de citocinas na resistência e suscetibilidade na leishmaniose cutânea murina infectados por Leishmania (L.) major
• Beneficiário: Luiza de Campos Reis
• Modalidade de apoio: Bolsas no Brasil - Doutorado