BACKGROUND AND PURPOSE
Chronic obstructive pulmonary disease (COPD) often tends to respond
poorly to glucocorticoid (GC) therapy. Reduced Histone deacetylase-2
(HDAC-2) activity is an important mechanism behind this GC
insensitivity. In this study, we investigated the effects of three
phosphodiesterase inhibitors (PDEIs), with anti-inflammatory propensity,
on cigarette smoke (CS) induced pulmonary inflammation and HDAC-2
activity.
EXPERIMENTAL APPROACH
Male C57BL/6 mice were exposed to cigarette smoke (CS) over the course
of 30 weeks. Administration of the PDEIs commenced from the
29th week and followed a schedule of once daily
treatments, 5 days a week, for 2 weeks. Roflumilast (ROF) was
administered intragastrically (5 mg·kg-1), while
pentoxifylline (PTX) (10 mg·kg-1) and theophylline
(THEO) (10 mg·kg-1) were administered
intraperitoneally, either alone or in combination with
a
GC (triamcinolone acetonide or TRI, 5 mg·kg-1, i.m.,
single injection). Lung morphometry, as well as the activity of HDAC-2,
pro-inflammatory cytokines and reactive oxygen species (ROS) were
assessed at the end of the 30 week course.