Insulin-Like Growth Factor-I as an Effector Element of the Cytokine IL-4 in the Development of a Leishmania major Infection
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-infecte...
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| Format: | Article |
| Language: | English |
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Wiley
2018-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2018/9787128 |
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| author | Luiza C. Reis Eduardo Milton Ramos-Sanchez Fabricio Petitto-Assis Audun H. Nerland Maria Hernandez-Valladares Frode Selheim Lucile Maria Floeter-Winter Hiro Goto |
| author_facet | Luiza C. Reis Eduardo Milton Ramos-Sanchez Fabricio Petitto-Assis Audun H. Nerland Maria Hernandez-Valladares Frode Selheim Lucile Maria Floeter-Winter Hiro Goto |
| author_sort | Luiza C. Reis |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-6974c5a52cae4e0cad8df317cd9bbcc1 |
| institution | OA Journals |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-6974c5a52cae4e0cad8df317cd9bbcc12025-08-20T02:23:55ZengWileyMediators of Inflammation0962-93511466-18612018-01-01201810.1155/2018/97871289787128Insulin-Like Growth Factor-I as an Effector Element of the Cytokine IL-4 in the Development of a Leishmania major InfectionLuiza C. Reis0Eduardo Milton Ramos-Sanchez1Fabricio Petitto-Assis2Audun H. Nerland3Maria Hernandez-Valladares4Frode Selheim5Lucile Maria Floeter-Winter6Hiro Goto7Instituto de Medicina Tropical de São Paulo, Universidade de São Paulo, IMTSP-USP, São Paulo, SP, BrazilInstituto de Medicina Tropical de São Paulo, Universidade de São Paulo, IMTSP-USP, São Paulo, SP, BrazilInstituto de Medicina Tropical de São Paulo, Universidade de São Paulo, IMTSP-USP, São Paulo, SP, BrazilDepartment of Clinical Science, University of Bergen, Bergen, NorwayDepartament of Biomedicine, University of Bergen, Bergen, NorwayDepartament of Biomedicine, University of Bergen, Bergen, NorwayDepartamento de Fisiologia, Instituto de Biociências, Universidade de São Paulo, São Paulo, SP, BrazilInstituto de Medicina Tropical de São Paulo, Universidade de São Paulo, IMTSP-USP, São Paulo, SP, BrazilCertain 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.http://dx.doi.org/10.1155/2018/9787128 |
| spellingShingle | Luiza C. Reis Eduardo Milton Ramos-Sanchez Fabricio Petitto-Assis Audun H. Nerland Maria Hernandez-Valladares Frode Selheim Lucile Maria Floeter-Winter Hiro Goto Insulin-Like Growth Factor-I as an Effector Element of the Cytokine IL-4 in the Development of a Leishmania major Infection Mediators of Inflammation |
| title | Insulin-Like Growth Factor-I as an Effector Element of the Cytokine IL-4 in the Development of a Leishmania major Infection |
| title_full | Insulin-Like Growth Factor-I as an Effector Element of the Cytokine IL-4 in the Development of a Leishmania major Infection |
| title_fullStr | Insulin-Like Growth Factor-I as an Effector Element of the Cytokine IL-4 in the Development of a Leishmania major Infection |
| title_full_unstemmed | Insulin-Like Growth Factor-I as an Effector Element of the Cytokine IL-4 in the Development of a Leishmania major Infection |
| title_short | Insulin-Like Growth Factor-I as an Effector Element of the Cytokine IL-4 in the Development of a Leishmania major Infection |
| title_sort | insulin like growth factor i as an effector element of the cytokine il 4 in the development of a leishmania major infection |
| url | http://dx.doi.org/10.1155/2018/9787128 |
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