Expression of multiple chemokine genes by a human mast cell leukemia.
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.
Selvan
R S
RS
Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710.
Butterfield
J H
JH
Krangel
M S
MS
D016207:Cytokines / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D007946:Leukemia, Mast-Cell / Q000235:genetics*; D008213:Lymphocyte Activation; D008407:Mast Cells / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D014407:Tumor Cells, Cultured
D016207:Cytokines; D005938:Glucocorticoids; D012333:RNA, Messenger