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

• Published in: Mediators of inflammation Vol. 2018; no. 2018; pp. 1 - 17
• Main Authors: Goto, Hiro, Selheim, Frode, Hernandez-Valladares, Maria, Nerland, Audun H., Petitto-Assis, Fabricio, Ramos-Sanchez, Eduardo Milton, Reis, Luiza C., Floeter Winter, L.
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 01-01-2018; Hindawi; John Wiley & Sons, Inc; Hindawi Limited
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Animals; Arginase; Blotting, Western; Cell activation; Comparative analysis; Cytokines; Diabetes; Electrophoresis, Polyacrylamide Gel; Evaluation; Gene expression; Health aspects; Immunology; Infection; Infections; Insulin; Insulin-like growth factor I; Insulin-Like Growth Factor I - genetics; Insulin-Like Growth Factor I - metabolism; Insulin-like growth factors; Interleukin 4; Interleukin-4 - pharmacology; Intracellular signalling; Kinases; Leishmania major; Leishmania major - metabolism; Leishmania major - pathogenicity; Leishmaniasis, Cutaneous - immunology; Leishmaniasis, Cutaneous - metabolism; Macrophages; Macrophages - drug effects; Macrophages - metabolism; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; mRNA; Nitric oxide; Parasites; Parasitic diseases; Parasitism; Phosphatidylinositol 3-Kinases - genetics; Phosphatidylinositol 3-Kinases - metabolism; Physiology; Polyamines; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; Protozoa; RAW 264.7 Cells; RNA; Rodents; siRNA; Transfection; Brazil; United States > US
• ISSN: 0962-9351; 1466-1861
• DOI: 10.1155/2018/9787128

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.