title: Effects of IL-17 on erythroid progenitors growth: involvement of MAPKs and GATA transcription factors.
abstract: 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.
authors.affiliation: Institute for Medical Research, University of Belgrade, Belgrade, Serbia. aleksandra@imi.bg.ac.rs
authors.forename: A
authors.initials: A
authors.lastname: Krstic
authors.forename: J
authors.initials: J
authors.lastname: Kocic
authors.forename: V
authors.initials: V
authors.lastname: Ilic
authors.forename: S
authors.initials: S
authors.lastname: Mojsilovic
authors.forename: I
authors.initials: I
authors.lastname: Okic-Dordevic
authors.forename: D
authors.initials: D
authors.lastname: Trivanovic
authors.forename: J F
authors.initials: JF
authors.lastname: Santibanez
authors.forename: G
authors.initials: G
authors.lastname: Jovcic
authors.forename: D
authors.initials: D
authors.lastname: Bugarski
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D015672:Erythroid Precursor Cells / Q000187:drug effects* / Q000502:physiology; D050980:GATA Transcription Factors / Q000032:analysis / Q000502:physiology*; D020381:Interleukin-17 / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA
chemical_list: D050980:GATA Transcription Factors; D020381:Interleukin-17