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
Luiza C ReisH Goto

Abstract

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.

References

Oct 1, 1991·Proceedings of the Society for Experimental Biology and Medicine·R R Gala
Sep 1, 1987·Annales De L'Institut Pasteur. Immunology·R M LocksleyK D Gardner
Oct 1, 1982·Analytical Biochemistry·L C GreenS R Tannenbaum
May 1, 1995·Molecular and Biochemical Parasitology·M KandpalB L Tekwani
Jan 1, 1995·Annual Review of Immunology·S L Reiner, R M Locksley
Feb 1, 1995·Endocrine Reviews·J I Jones, D R Clemmons
Mar 1, 1995·The Journal of Experimental Medicine·A H Shankar, R G Titus
Sep 14, 1994·Journal of Immunological Methods·I M CorralizaM Modolell
Jan 1, 1993·Annual Review of Physiology·W S Cohick, D R Clemmons
Jan 1, 1996·Pharmacology & Therapeutics·D A Weigent
Jan 1, 1996·Advances in Immunology·R KooijmanR Hooghe
Nov 1, 1996·Experimental Parasitology·P ScottB Hondowicz
Oct 28, 1998·Proceedings of the National Academy of Sciences of the United States of America·H GotoM Gidlund
Jan 21, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·D J MatthewsA N McKenzie
Sep 6, 2000·International Journal of Experimental Pathology·C M GomesC E Corbett
Mar 30, 2001·The Journal of Biological Chemistry·B NicholsonC L MacLeod
Aug 28, 2002·Immunity·Daniel B StetsonRichard M Locksley
Sep 23, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Murry W Wynes, David W H Riches
Aug 7, 2004·American Journal of Respiratory Cell and Molecular Biology·Nicola M HellerRobert P Schleimer
Sep 1, 2004·Growth Hormone & IGF Research : Official Journal of the Growth Hormone Research Society and the International IGF Research Society·Jan Frystyk
Jan 19, 2005·Acta Physiologica Scandinavica·A M ValverdeM Lorenzo
Jan 3, 2007·Brain, Behavior, and Immunity·Keith W KelleyRon Kooijman
Aug 21, 2008·American Journal of Physiology. Endocrinology and Metabolism·Luigi LaviolaFrancesco Giorgino
Jun 1, 2010·Immunity·Siamon Gordon, Fernando O Martinez
Apr 6, 2012·PloS One·Maria Fernanda Laranjeira da SilvaLucile M Floeter-Winter
Aug 23, 2012·Frontiers in Immunology·Rajiv Kumar, Susanne Nylén
Nov 23, 2013·Sub-cellular Biochemistry·Maria Fernanda Laranjeira da Silva, Lucile Maria Floeter-Winter
May 30, 2015·Experimental Cell Research·James P BarrettMarina A Lynch

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Citations

May 1, 2019·International Journal of Molecular Sciences·Deng-Ho Yang, Meng-Yin Yang

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Methods Mentioned

BETA
PCR
transfection
confocal microscopy

Software Mentioned

GraphPad
GraphPad Prism
[UNK]

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