Induction and secretion of the chemokines interleukin-8 and monocyte chemotactic protein-1 in human immature leukemia cell lines.
We investigated expression and secretion of the chemokines interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) in human myeloid cell lines. Quantitative determination by ELISA revealed a significant constitutive production of both chemokines in the cell lines HL-60 and NB-4 (>1000 pg/ml IL-8 and >400 pg/ml MCP-1 per million cells), while in the cell lines EOL-1, KASUMI-1 and KG-1 only 10-100 pg/ml IL-8 and MCP-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-fold 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, an 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 secretion in NB-4 cells, indicating the involvement of protein kinases in the signal transduction pathway which leads to enhanced chemokine secretion.
Steube
K G
KG
Department of Human and Animal Cell Cultures, DSMZ-German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany. kst@dsmz.de
Meyer
C
C
Drexler
H G
HG
D000001:Calcimycin / Q000494:pharmacology; D002273:Carcinogens; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005938:Glucocorticoids / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D016209:Interleukin-8 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D007476:Ionophores / Q000494:pharmacology; D007938:Leukemia / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000187:drug effects; D019311:Staurosporine / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate; D019284:Thapsigargin / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D002273:Carcinogens; D018932:Chemokine CCL2; D018925:Chemokines; D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D016209:Interleukin-8; D007476:Ionophores; D014409:Tumor Necrosis Factor-alpha; D000001:Calcimycin; D019284:Thapsigargin; D003907:Dexamethasone; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate