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Krstic, A; Kocic, J; Ilic, V; Mojsilovic, S; Okic-Dordevic, I; Trivanovic, D; Santibanez, JF; Jovcic, G; Bugarski, D.
Effects of IL-17 on erythroid progenitors growth: involvement of MAPKs and GATA transcription factors.
J Biol Regul Homeost Agents. 2012; 26(4):641-652
Web of Science
PubMed
- Co-authors Med Uni Graz
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Krstic Jelena
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- Abstract:
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Interleukin-17 is Th17 cell cytokine implicated in regulation of hematopoiesis and inflammation. Besides promoting granulopoiesis, we have previously shown that IL-17 also affects erythropoiesis stimulating the development of early erythroid progenitors, BFU-E, but suppressing, at least partly via p38 MAPK, the growth of late stage erythroid progenitors, CFU-E. The aim of the present study was to investigate the involvement of other MAPKs, JNK and ERK1/2, as well as GATA transcription factors, in IL-17-mediated effects on murine bone marrow erythroid progenitors. Data obtained by use of specific MAPKs inhibitors indicated that MEK1/2-ERK1/2 MAPK signaling mediates IL-17-induced CFU-E inhibition, as well as that JNK and/or MEK1/2-ERK1/2 MAPKs activation underlies IL-17-induced stimulation of BFU-E growth. Furthermore, Western blot analyses demonstrated no effect on early hematopoiesis transcription factor, GATA-2, and enhanced expression level of erythroid-specific factor GATA-1 in murine bone marrow cells after IL-17 stimulation, which in light of previous reports that GATA-1 overexpression inhibits erythroid differentiation, could be related to IL-17-mediated inhibition of CFU-E growth. Although, no contribution for p38, JNK and ERK MAPKs in IL-17-induced GATA-1 expression was shown, data obtained using specific inhibitors pointed to the role of JNK and MEK1/2-ERK1/2 in GATA-1 downregulation. Overall, obtained data gave an insight into the mechanisms by which IL-17 exerts its effects on erythropoiesis, implying the involvement of JNK and ERK MAPKs, as well as GATA-1, in IL-17-regulated growth of erythroid progentors.
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Animals -
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Cell Proliferation - drug effects
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Erythroid Precursor Cells - drug effects
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Erythroid Precursor Cells - physiology
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GATA Transcription Factors - analysis
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GATA Transcription Factors - physiology
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Interleukin-17 - pharmacology
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MAP Kinase Signaling System - physiology
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Male -
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Mice -
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Mice, Inbred CBA -
- Find related publications in this database (Keywords)
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IL-17
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erythropoiesis
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MAPK
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GATA