Resumen

Role of c-Myc and NkappaB in an in vitro model of occupational asthma Introduction: Occupational exposure to toluene diisocyanate (TDI) may cause asthma. TDI, a highly reactive industrial chemical with widespread use in the manufacture of polyurethane and plastics. Transcription factors induce expression of proteins involved in these events. Some authors suggest that exaggerated NF-kB activation perpetuates inflammatory mediators’ prouction in asthma. The expression of transcription factor c-Myc is deregulated in several diseases including cancer. However, its role in asthma has not been completely explored. Methods: A549 cells were grown in F-12 Ham’s medium containing 10% fetal bovine serum. Viability of these cells was determined by MTT assay. Cells were treated with TDI (100 microM -1 mM or DMSO (0.01%). Expression of NFkappaB and c-myc was evaluated by real time RT-PCR and Western Blot. EMSA assays to determine DNA binding of c-myc and NFkappaB were also performed. Results: Exposure to TDI reduces viability in A549 cells at 24 hours. The minimal concentration to induce effects was 200 microM. No differences in DNA binding of NkappaB or c-Myc were observed in TDI treated cells. However, expression of these factors and its target genes such as IL-13 or IL-8 changes slightly. Discussion: Cellular models of occupational asthma induced by chemical compounds such as TDI may help to understand the molecular mechanisms involved in disease development. The role of transcriptional factors is not completely understood. However it is clear that induction of certain genes and molecules contributes to exacerbate symptoms. At molecular level, our results indicate that further research is needed to evaluate other markers.