Alpha particles induce the production of interleukin-8 by human cells

The pulmonary microenvironment is a primary target for alpha particles like those emitted by inhaled radon and its progeny, While exposure to alpha pa rticles has recently been associated with the generation of extracellular a nd intracellular reactive oxygen species (ROS; Cancer Res. 57, 3963-3971, 1 997), little is known about how exposure to alpha particles mag affect the generation of oxidative stress-related mediators in the respiratory tract. Interleukin-8 (IL8) is a cytokine recognized for its potent role as a chemo attractant and activator of polymorphonuclear leukocytes, Oxidative stress can up-regulate expression of the gene that encodes IL8 (IL8) in a variety of cell types, In this study, we set out to investigate a potential linkage between the generation of ROS and production of ILS in alpha-particle-irra diated normal human lung fibroblasts, ELISA revealed that exposure of the f ibroblasts to low doses of alpha particles (3.6-19 cGy) caused significant increases in generation of the IL8 protein as early as 30 min after irradia tion. Northern blot analyses revealed that such increases were associated w ith increased IL8 mRNA levels, Cells exposed to alpha particles in the pres ence of antioxidants, i.e. superoxide dismutase and dimethyl sulfoxide, res ulted in significant decreases in extracellular IL8 protein levels. Similar results were obtained with cells treated with dexamethasone, an inhibitor of transcription, Our results indicate that alpha-particle-induced increase s in production of ns occur temporally in parallel with elevated production of ROS, Conceivably, such production of ILS induced by a particles may con tribute to an inflammatory response in the lower respiratory tract. Additio nally, the promitogenic effects of IL8 may be a factor in hyperplastic resp onses in the airway epithelial cells to inhaled radon and radon progeny and perhaps other stresses associated with ROS, (C) 1999 br Radiation Research Society.