Multiple regulation of constitutive and induced interleukin 8 secretion in human myelomonocytic cell lines

Secretion of interleukin 8 (IL-8) and its regulation was investigated in myelomonocytic leukaemia cell lines. Quantification by ELISA revealed a constitutive production in the cell lines HL-60, ML-2, MONO-MAC-6 and MUTZ-3 ranging between 1500 and ca. 5000 pg/ml IL-8 per million cells. No measurable IL-8 was detected in the culture medium of MONO-MAC-1 and THP-1. Stimulation with lipopolysaccharide (LPS) or tetradecanoyl phorbol acetate (TPA) significantly increased the IL-8 level secreted by all cell lines; the best producers were TPA-treated MONO-MAC-6 and MUTZ-3 cultures, generating more than 50 000 pg/ml IL-8. Also the calcium ionophore A-23187, IL-13, macrophage colony-stimulating factor (M-CSF), thapsigargin, an inhibitor of the Ca(2+)-ATPase, and tumour necrosis factor-alpha (TNF-alpha) strongly enhanced the IL-8 production in MONO-MAC-6 cells. The glucocorticoid dexamethasone and the protein kinase inhibitor staurosporine distinctively inhibited the IL-8 production of MONO-MAC-6 cells. Thus, our results demonstrate a strong constitutive IL-8 secretion in human myelomonocytic leukaemia cell lines; the variety of different modulators affecting IL-8 production leads to the suggestion of a multiple regulation of IL-8 expression and secretion.