Biomaterial Database

[Bacillus Calmette-Guérin enhances the function of human nature killer cells by inducing IL-12 production and IL-12R expression]. 2009

Hui Zhou, and Yan-ying Fan, and Chang-you Wu

Department of Clinical Laboratory, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China. jzhouhui@126.com

OBJECTIVE To study the effect and mechanism of BCG on human nature killer cells. METHODS PBMC or purified NK cells were isolated from normal human peripheral blood with negative anti-Mycobacterium tuberculosis antibody and cultured with BCG, IL-12, BCG plus IL-12 and BCG plus anti-IL-12R beta 1 mAb (2B10), respectively. The levels of IFN-gamma and IL-12p40 in the culture supernatants were measured by ELISA. The frequency of IFN-gamma and granzyme B producing cells were analyzed by ELISpot. The cytolytic activity was detected by MTT reduction assay. The surface expression of IL-12R beta 1 on NK cells was detected by flow cytometry. RESULTS BCG significantly induced IFN-gamma production by PBMC in a dose-dependent manner. When PBMC was stimulated with BCG, the frequency of granzyme B producing cells was higher than that in unstimulated PBMC (P<0.05). BCG enhanced the cytotoxic activity of PBMC. BCG alone didn't induce IFN-gamma production by purified NK cells, but it can augment IL-12-induced IFN-gamma production by purified NK cells. The cytotoxic activities of BCG-stimulated and unstimulated purified NK cells were not significantly different (P>0.05). BCG induced IL-12 production by PBMC in a dose-dependent manner and enhanced IL-12R beta 1 expression on different subsets of NK cells. Blocking the effect of IL-12 by anti-IL-12R beta 1 mAb (2B10) inhibited BCG-induced IFN-gamma production and granzyme B releasing by PBMC. CONCLUSIONS BCG can indirectly promote biologic activity of NK cells and the production of endogenous IL-12 combined with up-regulation IL-12R beta 1 expression on the surface of NK cells is a part of the mechanisms of IL-12 on human NK cells.

UI	MeSH Term	Description	Entries
D007371	Interferon-gamma	The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES.	Interferon Type II,Interferon, Immune,gamma-Interferon,Interferon, gamma,Type II Interferon,Immune Interferon,Interferon, Type II
D007694	Killer Cells, Natural	Bone marrow-derived lymphocytes that possess cytotoxic properties, classically directed against transformed and virus-infected cells. Unlike T CELLS; and B CELLS; NK CELLS are not antigen specific. The cytotoxicity of natural killer cells is determined by the collective signaling of an array of inhibitory and stimulatory CELL SURFACE RECEPTORS. A subset of T-LYMPHOCYTES referred to as NATURAL KILLER T CELLS shares some of the properties of this cell type.	NK Cells,Natural Killer Cells,Cell, NK,Cell, Natural Killer,Cells, NK,Cells, Natural Killer,Killer Cell, Natural,NK Cell,Natural Killer Cell
D009163	Mycobacterium bovis	The bovine variety of the tubercle bacillus. It is called also Mycobacterium tuberculosis var. bovis.	BCG,Calmette-Guerin Bacillus
D005786	Gene Expression Regulation	Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.	Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D045744	Cell Line, Tumor	A cell line derived from cultured tumor cells.	Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines
D053707	Receptors, Interleukin-12	Cell surface receptors for INTERLEUKIN-12. They exist as dimers of beta 1 and beta 2 subunits. Signaling from interleukin-12 receptors occurs through their interaction with JANUS KINASES.	IL-12 Receptors,Interleukin-12 Receptors,IL-12 Receptor,Interleukin-12 Receptor,Receptor, Interleukin-12,IL 12 Receptor,IL 12 Receptors,Interleukin 12 Receptor,Interleukin 12 Receptors,Receptor, IL-12,Receptor, Interleukin 12,Receptors, IL-12,Receptors, Interleukin 12
D018664	Interleukin-12	A heterodimeric cytokine that plays a role in innate and adaptive immune responses. Interleukin-12 is a 70 kDa protein that is composed of covalently linked 40 kDa and 35 kDa subunits. It is produced by DENDRITIC CELLS; MACROPHAGES and a variety of other immune cells and plays a role in the stimulation of INTERFERON-GAMMA production by T-LYMPHOCYTES and NATURAL KILLER CELLS.	Edodekin Alfa,IL-12,Natural Killer Cell Stimulatory Factor,Cytotoxic Lymphocyte Maturation Factor,IL 12,IL-12 p70,IL12,Interleukin 12,Interleukin-12 p70,Interleukin 12 p70