S14 Histone deacetylase activity is reduced in COPD subjects during rhinovirus induced exacerbations

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Abstract

Introduction and Objectives

Histone deacetylase (HDAC) enzymes have a role in suppressing inflammatory gene transcription. There is evidence for reduced HDAC activity in COPD which correlates with the severity of airflow obstruction. Increased inflammation found during exacerbations of COPD may result from a reduction in HDAC activity but this has not been studied in virus induced exacerbations. We sought to investigate HDAC activity following rhinovirus infection in an experimental model of COPD exacerbations.

Methods

Experimental rhinovirus challenge was performed in GOLD stage II COPD subjects and non-obstructed control smokers and non-smokers. Rhinovirus infection was confirmed with quantitative PCR performed on nasal lavage and sputum samples collected at baseline and days 3, 5, 9, 12, 15, 21 and 42 post virus inoculation. Sputum macrophages were isolated by adhesion and HDAC2 isoenzyme immunoprecipitated, prior to performing a HDAC activity assay.

Results

11 non-smokers (NS), 10 smokers (Smk) and 9 COPD subjects were recruited. The mean (SEM) % predicted baseline FEV1 was 103 (4), 98 (4) and 69 (2)% for NS, Smk and COPD respectively. At baseline there was no difference in HDAC2 activity between the three study groups, the geometric mean (95% CI) activity was NS 22.39 (12.45 to 40.25); Smk 22.91 (18.28 to 28.71) and COPD 48.98 (26.04 to 92.13) (p=0.095). Following rhinovirus infection, in NS HDAC2 activity increased, in Smk it remained largely unchanged and there was a fall from baseline levels in COPD subjects at all time points, Abstract S14 figure 1.

Conclusions

HDAC2 activity was not reduced in stable COPD subjects compared to controls. This may reflect the mild disease state of the study population. During a rhinovirus induced exacerbation HDAC2 activity fell in COPD subjects, this represents a potential mechanism of excessive inflammation. The same pattern is not seen in control subjects.

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