title: HMBOX1, homeobox transcription factor, negatively regulates interferon-γ production in natural killer cells.
abstract: HMBOX1 is a new member of homeobox family and predicted to be a transcriptional repressor, its function in NK cells is completely unclear. Previously we found that overexpression of HMBOX1 downregulated mRNA level of IFN-γ in NK cells during our gene screening work. In present study, we investigate the relationship between HMBOX1 and IFN-γ in detail. Firstly, we describe the properties of HMBOX1 gene transcription in activated NK cells, and found that the transcriptional levels of HMBOX1 were significantly decreased in NK cells after activated by IL-2, IL-15 and IL-12, which was opposite to the expression profile of IFN-γ. Subsequently, over-expression of HMBOX1 significantly inhibited the expression and production of IFN-γ in NK cells in response to the stimulation of tumor cell K562 or PMA/ionomycin. Additionally, by luciferase reporter assay, HMBOX1 displayed suppressive effect on the transcription activity of IFN-γ promoter. These findings indicated that HMBOX1 may function as a negative regulator of IFN-γ in NK cells.
authors.affiliation: School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China.
authors.forename: Longyan
authors.initials: L
authors.lastname: Wu
authors.forename: Cai
authors.initials: C
authors.lastname: Zhang
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zheng
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Tian
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
mesh_terms: D016207:Cytokines / Q000276:immunology; D015536:Down-Regulation; D005434:Flow Cytometry; D057809:HEK293 Cells; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics*; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*; D008156:Luciferases / Q000235:genetics; D008213:Lymphocyte Activation / Q000276:immunology; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
chemical_list: D016207:Cytokines; C512050:HMBOX1 protein, human; D018398:Homeodomain Proteins; D007371:Interferon-gamma; D008156:Luciferases