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Expression of multiple chemokine genes by a human mast cell leukemia
R S Selvan1, J H Butterfield, M S Krangel
1Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710.
Insights
Human mast cells (HMC-1) produce multiple chemokines, key inflammatory mediators. Glucocorticoids partially inhibit this production, suggesting distinct regulatory pathways compared to T-cells.
Area of Science:
- Immunology
- Cell Biology
Background:
- Chemokines are crucial cytokines mediating inflammatory responses.
- Human mast cell leukemia line (HMC-1) is investigated as a source of chemokines.
Purpose of the Study:
- To identify chemokines produced by HMC-1 cells.
- To investigate the regulation of chemokine expression by phorbol ester and glucocorticoids.
- To compare chemokine gene regulation in mast cells versus T-cells.
Main Methods:
- HMC-1 cells were treated with phorbol ester to induce chemokine expression.
- Quantitative analysis of chemokine transcripts and protein secretion.
- Treatment with methyl-prednisolone to assess glucocorticoid effects.
- Comparison with chemokine expression in activated T-cells.
Main Results:
- HMC-1 cells secrete multiple chemokines, including I-309, MCP-1, MIP-1α, MIP-1β, RANTES, and IL-8.
- Phorbol ester up-regulates both chemokine transcript levels and protein secretion, requiring de novo protein synthesis.
- Methyl-prednisolone selectively reduces MCP-1 transcripts in HMC-1 cells, unlike its broader effects on T-cells.
- Glucocorticoid effects are attributed to transcriptional inhibition.
Conclusions:
- Human mast cells are significant sources of various chemokines.
- Glucocorticoids exhibit selective inhibition of specific chemokines in mast cells.
- Mast cell and T-cell chemokine expression pathways are distinct and differentially regulated.
Abstract:
The chemokines are a large group of cytokines that are recognized to be important mediators of inflammation. In this study we show that the human mast cell leukemia line HMC-1 is a source of multiple chemokines, including I-309, monocyte chemoattractant protein 1, macrophage inflammatory protein-1 alpha, macrophage inflammatory protein-1 beta, RANTES, and interleukin-8. I-309 and MCP-1 transcripts are expressed at low levels in unstimulated HMC-1. However, phorbol ester treatment up-regulates these and other chemokine transcript levels and also up-regulates chemokine protein synthesis and secretion. Induction of chemokine transcripts in HMC-1 requires de novo protein synthesis. We compared the effects of anti-inflammatory glucocorticoids on the expression of chemokine genes in HMC-1 to their effects in activated T-cells. We find that methyl-prednisolone reduces MCP-1 but not other chemokine transcripts in HMC-1, even though there are distinct and more general effects on chemokine transcripts in activated T-cells. These effects are attributed to inhibition of transcription rather than transcript stability. Our results suggest that human mast cells may be a source of multiple chemokines, that glucocorticoids may inhibit the expression of only a subset of these chemokines, and that mast cells and T-cell chemokine expression may occur via distinct regulatory pathways.