Expression of Histone Deacetylates ( HDAC3) and Phosphorylated-cAMP Response Element-Binding (P-CREB) in Bronchial Bipopsies of Asthmatics

Chrornatin modifìcation plays a role in inflammatory gene regulation in asthma. Histone acetylation by acetyltransferases (HATs) is associated with increased inflammatory gene transcription, hypoacetylation by histone deacetylases (HDACs) is associated with suppression of gene expression.The increase in HAT and the reduction of HDACs activities may underlie the increased expression of inflammatory genes, partly reversed by treatment with inhaled steroids (JS). We evaluated whether branchia l epithelium and submucosa inftammation in untreated, IS treated, and steroiddependent asthmatics (SDA) was associated with an increased expression of HATs, including CREB-Binding Protein (CPB) and P-CREB, or with a reduction ofHDACs expression including HDACI, 2, and 3. We evaluated the expression ofthese molecules in branchia! biopsies of controls (C), untreated (UA), IS treated (ICS) and SDA. HDACI and 2 expression was similar in ali groups while HDAC3 expression was higher in C than in the other groups (C vs. UA p=0,0003, C vs. SDA p=0,0008 and C vs. ICS p=0,003). CBP expression was similar in ali groups while P-CREB expression was reduced in C and in ICS than in UA and in SDA (C vs. UA p=0,0004, and C vs. SDA p= 0,0036). This study demonstrates that the expression of P-CREB and HDAC3 is related to the severity of the disease an d that P-CREB expression is down regulated by the IS therapy in ICS.