Interleukin-18 enhances cytokine secretion by monocytes activated through direct contact with T lymphocytes / 第二军医大学学报
Academic Journal of Second Military Medical University
;
(12): 157-161, 2010.
Artigo
em Chinês
| WPRIM
| ID: wpr-840651
ABSTRACT
Objective:
To study whether interleukin (IL)-18 is involved in the activation of monocytes through direct contact with T cells and the related intracellular mechanism.Methods:
T cells and monocytes were isolated and purified from the peripheral blood of healthy donors by magnetic beads. Phytohemagglutinin (PHA) pre-stimulated T cells were fixed by 1% paraformaldehyde and were then co-cultured with monocytes at a T cell monocyte ratio of 41. TNF-α and IL-18 levels in the supernatants were assayed by ELISA. Expression of IL-18 receptor α chain (IL-18Rα) on the surface of monocytes was analyzed by flow cytometry.Results:
Monocytes activated by PHA-stimulated T cells produced significantly more TNF-α than by unstimulated T cells; non-cultured T cells or monocytes hardly produced any TNF-α. Upon direct cellular contact, PHA prestimulated T cells also up-regulated IL-18Rα expression on the surface of monocytes and induced IL-18 production in monocytes, which could be suppressed by nuclear factor (NF)-κB inhibitor (N-acetyl-L-cysteine, NAC) or phosphatidyl-inositol (PT) 3 kinase inhibitor (LY294002), but not by mitogen activated protein kinase (MAPK) inhibitor (SB203580). Neutralizing anti-IL-18 monoclonal antibody dose-dependently inhibited the production of TNF-α by monocyte-stimulated T cells. IL-18 failed to induce TNF-α production by cultured monocytes alone, while dose-dependently enhanced TNF-α production in monocyte-stimulated T cells, which could be inhibited by NAC or LY294002, but not by SB203580.Conclusion:
By direct cellular contact T cells can stimulate monocytes to produce TNF-α and IL-18, up-regulate IL-18 receptor expression in monocytes, and activate intracellular NF-κB and PI3 kinase pathways. IL-18 can enhance T cell ability to stimulate TNF-α production by monocytes, which is dependent on the activation of NF-κB and PI3 kinase pathways.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Idioma:
Chinês
Revista:
Academic Journal of Second Military Medical University
Ano de publicação:
2010
Tipo de documento:
Artigo
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