IL-4 ENHANCES IL-3 AND IL-8 GENE-EXPRESSION IN A HUMAN LEUKEMIC MAST-CELL LINE

We examined the capacity of interleukin (IL)-4 to induce or enhance th e expression of certain cytokines in resting and activated cells of th e HMC-1 human leukemic mast cell line. The HMC-1 mast cells were cultu red with or without recombinant human IL-4 and then activated with the calcium ionophore ionomycin, Stimulation of non-IL-4-treated cells wi th ionomycin (10 mu M) for periods of 30 min to 8 hr induced expressio n of mRNA encoding IL-3, IL-4 and IL-8 but was without effect on level s of mRNA for tumour necrosis factor (TNF)-alpha or beta-actin. Cultur e of the cells with IL-4 (100 ng/ml) for 24 hr led to a small increase in resting levels of mRNA for IL-3 and IL-8 but not for IL-4, TNF-alp ha or beta-actin. More notably, the IL-4 treatment produced a pronounc ed elevation of mRNA for IL-3 and IL-8 when the cells were subsequentl y activated with ionomycin. The IL-4 treatment produced a negligible e ffect on IL-4 mRNA, and no effect on TNF-alpha or beta-actin mRNA leve ls in ionomycin-activated cells. Quantitation of cDNA by competitive p olymerase chain reaction (PCR) revealed that the IL-4 treatment produc ed a sixfold increase in ionomycin-induced levels of cellular IL-3 mRN A, a fourfold increase in induced IL-8 mRNA and less than a twofold in crease in induced IL-4 mRNA. The IL-4 treatment led to a 15- to 20-fol d increase in ionomycin-induced secretion of IL-3 product and a doubli ng of induced IL-8 product. These effects of IL-4 were not associated with increased mast cell numbers. We conclude that IL-4 alone is a wea k activator of IL-3 and IL-8 gene expression in mast cells, but is abl e to enhance activation signals in stimulated mast cells leading to tr anscription and secretion of these two cytokines.