Downregulation of microRNA-24 and -181 parallels the upregulation of IFN-γ secreted by activated human CD4 lymphocytes.
IFN-γ is a cytokine with important roles in the innate and adaptive immune responses. This cytokine is secreted by activated T cells, NK cells and macrophages. Studies on the regulation of human IFN-γ expression had been previously focused on the promoter region. Consequently, the role of microRNAs (miRs) in this regulation has not been investigated yet. As miR-24 and miR-181 were found to have potential target sites in IFN-γ mRNA 3'UTR, we assessed their impact on IFN-γ expression by co-stimulating PB CD4+ T cells with anti-CD3, anti-CD28, IL-12, and IL-18. This co-stimulation cocktail induced an abundant secretion of IFN-γ together with a down-regulation of miR-24, and miR-181. Existence of a link between these two phenomena was further substantiated by transfection and transduction assays that showed that these two miRs negatively regulate IFN-γ expression by directly binding to their target sites in the mRNA. Thus, identifying target sites for miR-24 and miR-181 in IFN-γ-3'UTR points to a novel regulatory mechanism of this crucial gene.
Laboratory of Experimental Hematology, Institut Jules Bordet, Université Libre de Bruxelles, 121, Boulevard de Waterloo, 1000 Bruxelles, Belgium.
Hussein
H
Fayyad-Kazan
Department of Biochemistry, Laboratory of Immunology, EDST-PRASE, Lebanese University, Faculty of Sciences, Hadath-Beirut, Lebanon.
Eva
E
Hamade
Laboratory of Experimental Hematology, Institut Jules Bordet, Université Libre de Bruxelles, 121, Boulevard de Waterloo, 1000 Bruxelles, Belgium.
Redouane
R
Rouas
Laboratory of Clinical Cell Therapy (LTCC), Hôpital Erasme, Université libre de Bruxelles (ULB), 808, Route de Lennik, 1070 Brussels, Belgium.
Mehdi
M
Najar
Laboratory of Membrane Transport Biology, IBMM (Institute for Molecular Biology and Medicine), Université Libre de Bruxelles, 12 Rue des Professeurs Jeener et Brachet, 6041 Gosselies, Belgium.
Mohammad
M
Fayyad-Kazan
Department of Biochemistry, Laboratory of Immunology, EDST-PRASE, Lebanese University, Faculty of Sciences, Hadath-Beirut, Lebanon.
Nabil
N
El Zein
Department of Biochemistry, Laboratory of Immunology, EDST-PRASE, Lebanese University, Faculty of Sciences, Hadath-Beirut, Lebanon.
Rim
R
ElDirani
Department of Biochemistry, Laboratory of Immunology, EDST-PRASE, Lebanese University, Faculty of Sciences, Hadath-Beirut, Lebanon.
Nader
N
Hussein
Department of Biochemistry, Laboratory of Immunology, EDST-PRASE, Lebanese University, Faculty of Sciences, Hadath-Beirut, Lebanon.
Maya
M
Fakhry
Department of Biochemistry, Laboratory of Immunology, EDST-PRASE, Lebanese University, Faculty of Sciences, Hadath-Beirut, Lebanon.
Carine
C
Al-Akoum
Laboratory of Experimental Hematology, Institut Jules Bordet, Université Libre de Bruxelles, 121, Boulevard de Waterloo, 1000 Bruxelles, Belgium.
Arsène
A
Burny
Laboratory of Experimental Hematology, Institut Jules Bordet, Université Libre de Bruxelles, 121, Boulevard de Waterloo, 1000 Bruxelles, Belgium.
Philippe
P
Martiat
Department of Biochemistry, Laboratory of Immunology, EDST-PRASE, Lebanese University, Faculty of Sciences, Hadath-Beirut, Lebanon. Electronic address: bbadran@ulb.ac.be.
Bassam
B
Badran
D020413:3' Untranslated Regions; D000906:Antibodies / Q000494:pharmacology; D001483:Base Sequence; D001665:Binding Sites; D018106:CD28 Antigens / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D017252:CD3 Complex / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D002469:Cell Separation; D005786:Gene Expression Regulation; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D018664:Interleukin-12 / Q000494:pharmacology; D020382:Interleukin-18 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology; D008969:Molecular Sequence Data; D061251:Primary Cell Culture; D015398:Signal Transduction
D020413:3' Untranslated Regions; D000906:Antibodies; D018106:CD28 Antigens; D017252:CD3 Complex; C000589760:IL18 protein, human; D020382:Interleukin-18; C543845:MIRN24 microRNA, human; C540193:MIrn181 microRNA, human; D035683:MicroRNAs; D018664:Interleukin-12; D007371:Interferon-gamma
Activated CD4 T lymphocyte; IFN-γ; microRNA