Abstract
Background: Airway inflammation is a primary component of asthma. However, the biological mechanism(s) controlling the increased inflammatory response in the airways in asthma is unknown. Inflammation-associated gene transcription is, in part, controlled by histone acetylation which is mediated by histone acetyltransferases (HATs) and histone deacetylases (HDACs). This project was designed to determine differences in HAT and HDAC gene expression in asthma versus non-asthma. Methods: Using a two group unpaired design individuals with (mild) asthma (n = 9) and individuals without asthma (n = 16) completed a medical health questionnaire, pulmonary function tests, and airway fluid sampling (sputum induction). Gene expression (Quantitative PCR) was performed on HATs: Activating Transcription factor-2 (ATF-2), Steroid receptor co-activator 1 (SRC-1), Transcription initiating factor-2 (TIF-2), CREB Binding protein (CBP), p300, p300/CBP associated factor (PCAF) and HDACs 1 through to 6. Results: As expected a lower expression of all HDACs was seen in the asthma group, compared to the non-asthma group. In particular there was a 15-fold lower expression in HDAC 5 (p less than 0.01) and a 4.6-fold lower expression in HDAC 1 (p less than 0.01). However; somewhat unexpectedly a decrease in the expression of HAT enzymes was also observed, in the asthma group, compared to the non-asthma group. There being a 3.6- fold lower expression in PCAF (p less than 0.04) and a 2.1-fold lower expression of p300 (p less than 0.08). No statistically significant changes were observed for the other enzymes. Conclusions: The role histone acetylation plays in asthma, is not well understood; however our results indicate that the HAT and HDAC enzymes are likely contributors to the overall inflammatory response observed in asthma.