Induction and Secretion of the Chemokines Interleukin-8 and Monocyte Chemotactic Protein-1 in Human Immature Leukemia Cell Lines

摘要

We investigated expression and secretion of the chemokines interlekin-8 (IL-8) and monocyte chemotactic protein-a (MCP-1) in human myeloid cell lines.Quantitative determination by ELISA revealed a significant constitutive production f both chemokines in the cell lines HL-60 and NB-4 (>1000 pg/ml IL-8 and >400 pg/mlKASUMI-1 and KG-1 only 10-100 pg/ml IL-8 and ECP-1 were detected.Tetradecanoyl phorbol acetate (TPA) strongly increased the IL-8 and MCP-1 amounts in the culture supernatants of all five cell lines.The TPA-induced NB-4 produced the largest amounts of both chemokines (>40,000 pg/ml).The strongest induction was seen in EOL-1 (>100-folk increase). Besides TPA,tumor necrosis factor-#alpha# (TNF#alpha#) also distinctively enhanced IL-8 and MCP-1 production.The calcium ionophore A-23187 and thapsigargin,and inhibitor of the Ca~(2+)-ATPase, differentially induced IL-8 and MCP-1 secretion in the cell lines investigated,suggesting that,at least in some cell lines,intracellular free Ca~(2+) might be important for chemokine secretion.Dexamethasone significantly prevented the IL-8 and MCP-1 production of stimulated cells,emphasizing the potent anti-inflammatory property of glucocorticoids.Similarly,the protein kinase inhibitor staurosporine clearly decreased the TPA-induced chemokine scretion in NB-4 cells,indicating the involvement of protein kinases in the sigmal transduction pathway which leads to enhanced chemikine secretion.