Interleukin-18 enhances cytokine secretion by monocytes activated through direct contact with T lymphocytes
10.3724/SP.J.1008.2009.00157
- Author:
Hong HUO
1
Author Information
1. Department of Nephrology
- Publication Type:Journal Article
- Keywords:
Cell contact;
Interleukin-18;
Monocytes macrophages;
Signal transduction;
T lymphocytes
- From:
Academic Journal of Second Military Medical University
2010;30(2):157-161
- CountryChina
- Language:Chinese
-
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 4:1. 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.
