EXPRESSION OF MULTIPLE CHEMOKINE GENES BY A HUMAN MAST-CELL LEUKEMIA

The chemokines are a large group of cytokines that are recognized to b e 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 infl ammatory protein-1 alpha, macrophage inflammatory protein-1 beta, RANT ES, and interleukin-8. I-309 and MCP-1 transcripts are expressed at lo w levels in unstimulated HMC-1. However, phorbol ester treatment up-re gulates these and other chemokine transcript levels and also up regula tes chemokine protein synthesis and secretion. Induction of chemokine transcripts in HMC-1 requires de novo protein synthesis. We compared t he effects of anti-inflammatory glucocorticoids on the expression of c hemokine genes in HMC-1 to their effects in activated T cells. We find that methyl prednisolone reduces MCP-1 but not other chemokine transc ripts in HMC-1, even though there are distinct and more general effect s on chemokine transcripts in activated T-cells. These effects are att ributed to inhibition of transcription rather than transcript stabilit y. Our results suggest that human mast cells may be a source of multip le chemokines, that glucocorticoids may inhibit the expression of only a subset of these chemokines, and that mast cells and T-cell chemokin e expression may occur via distinct regulatory pathways.