Glucocorticoid receptors must be deacetylated by HDAC2 to block NF-κB-driven gene expression.

A new study by Ito and colleagues on page 7 may help explain why patients with a severe lung disease called chronic obstructive pulmonary disease (COPD) fail to respond to steroid treatment. Ito and colleagues show that steroids require the enzyme HDAC2 (histone deacetylase 2) to block the inflammatory transcription factor NF-κB. In patients with COPD, HDAC2 activity is reduced, rendering cells impervious to the soothing effects of steroids.

Steroids called glucocorticoids (GCs) are powerful antiinflammatory drugs used to treat chronic inflammatory disorders such as asthma and inflammatory bowel disease. But these drugs don't work in patients with COPD—a chronic inflammatory disease of the lungs linked to cigarette smoking.

When working properly, GCs calm inflammation in two ways. They bind to the cytoplasmic glucocorticoid receptor (GR), which then binds to NF-κB and prevents...

The Rockefeller University Press
2006
The Rockefeller University Press
2006
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