Chemical induction of interleukin-8, a proinflammatory chemokine, in human epidermal keratinocyte cultures and its relation to cytogenetic toxicity.

摘要: Tumor promoters, proinflammatory cytokines, endotoxins, and protein synthesis inhibitors can modulate cell cycle kinetics of various types, stimulate production reactive oxygen species, induce keratinocytes to produce interleukin-8 (IL-8), a potent chemotactant for polymorphonuclear neutrophils T lymphocytes. The aim this study was determine whether perturbations cytogenetic responses correlated with the induction IL-8 expression. Cultures primary human were grown in serum-free medium 5 μmol/L bromodeoxyuridine label DNA exposed either phorbol-13-myristate-12-acetate (PMA) (0.0001–100 ng/ml), cycloheximice (CHX) (0.01–50 μg), lipopolysaccharide (0.1–100 μg/ml), tumor necrosis factor-α (TNFα) (3.13–50 or interleukin-1α (IL-1α) (1–182 pg/ml). Metaphase chromosome preparations stained by fluorescence-plus-Giemsa technique differentiate sister chromatids. For production, 70% confluency then chemicals 24 h. Immunoreactive quantitated from supernatants ELISA. With exception benzo(a)pyrene used as positive control, none agents induced chromatid exchanges. However, PMA TNFα that coincided significant inhibition. IL-1α had no effect on endpoints, yet stimulated 6.3-fold increase IL-8. CHX inhibited progression mitotic activity at concentrations 200 times lower than required induction; however, puromycin (0.31–10 another inhibitor, did not At all tested, reduced index ∼45%, slowed ∼3.5 h, flat, albeit large, response ≥12.5 ng/ml. These agent-specific patterns suggest is always inevitable result genetic damage.