Academic Journal
Insulin-Like Growth Factor-I as an Effector Element of the Cytokine IL-4 in the Development of a Leishmania major Infection
| Title: | Insulin-Like Growth Factor-I as an Effector Element of the Cytokine IL-4 in the Development of a Leishmania major Infection |
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| Authors: | Luiza C. Reis, Eduardo Milton Ramos-Sanchez, Fabricio Petitto-Assis, Audun H. Nerland, Maria Hernandez-Valladares, Frode Selheim, Lucile Maria Floeter-Winter, Hiro Goto |
| Source: | Mediators of Inflammation, Vol 2018 (2018) |
| Publisher Information: | Hindawi Limited, 2018. |
| Publication Year: | 2018 |
| Collection: | LCC:Pathology |
| Subject Terms: | Pathology, RB1-214 |
| More Details: | 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. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 0962-9351 1466-1861 |
| Relation: | https://doaj.org/toc/0962-9351; https://doaj.org/toc/1466-1861 |
| DOI: | 10.1155/2018/9787128 |
| Access URL: | https://doaj.org/article/6974c5a52cae4e0cad8df317cd9bbcc1 |
| Accession Number: | edsdoj.6974c5a52cae4e0cad8df317cd9bbcc1 |
| Database: | Directory of Open Access Journals |
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| ISSN: | 09629351 14661861 |
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| DOI: | 10.1155/2018/9787128 |
| Published in: | Mediators of Inflammation |
| Language: | English |