Zinc-oxide (ZnO) is a major occupational and environmental air toxin. We have shown that single and repeated controlled exposure to ZnO in healthy individuals, results in differential increases in leukocytes, and in the protein level of TNFa, IL-I.B, 1L-6, and 1L-8, in the airway. The mechanisms of this inflammatory response, and the effect of ZnO exposure on individuals with asthma are unknown. We hypothesize that there will be a different pattern of gene expression in single compared to repeated ZnO exposure, and in healthy individuals compared to individuals with asthma. We therefore measured gene expression by quantitative real-time RT-PCR in airway cells (sputum-induction) from healthy individuals and individuals with asthma who had both one and two (consecutive day) ZnO exposures (10 mg m3; 30 min). Genes involved in toxin-induced acute airway inflammation, chronic asthma-associated airway inflammation and anti-inflammatory processes, including IL-1Beta, IL-5, IL-6, IL-8, IL-10, IL-13, ENA-78, TNFa, CD1 1b, HSP-72, HO1 and NFKB, were investigated. We found that in the healthy group, IL-13gene expression was increased following one ZnO exposure, and IL-10 was increased following two ZnO exposures. In the asthma group, IL-1Beta, IL-8, IL-13, HO1 and HSP-72 were increased after one ZnO exposure, and NFKB was decreased following two ZnO exposures. These data indicate a differential gene expression response for single compared to repeated ZnO exposure, and for healthy individuals compared to individuals with asthma. However, IL-13 appears to be involved in the acute airway response to ZnO in both subject groups.
American Journal of Respiratory and Critical Care Medicine, 2003 International Conference, The American Thoracic Society, Seattle, WA, May 16-21, 2003
Center for Occupational and Environmental Health, University of Califorinia, Berkeley, California