We hypothesized that the peculiar mixed interleukin-4 (IL-4/Th2) and interferon gamma INF-γ (INF-γ/Th1) inflammatory milieu found in the airways of patients with aspirin-exacerbated respiratory disease (AERD) is responsible for the altered regulation of the IL-1β/IL-1RI-/EP<sub>2</sub>/COX-2 autocrine loop also found in these patients.
The cause of AERD have remained unclear, however the decrease in the production of PGE2 caused by the reduction in COX-2 activity is considered to main pathological mechanism of AERD.
The pathogenesis of aspirin-exacerbated respiratory disease (AERD) is characterized by the low expression of cyclooxygenase-2 (COX-2) in airway epithelia, which decreases the production of prostaglandin E<sub>2</sub> (PGE<sub>2</sub>).
We hypothesized that the 2 reported alterations in aspirin-exacerbated respiratory disease (AERD), reduced expression/production of COX-2/prostaglandin (PG) E2 and diminished expression of E-prostanoid (EP) 2 receptor, are closely linked.
Treatment of the fibroblasts with trichostatin A, a histone deacetylase inhibitor, significantly increased EP2 receptor mRNA in fibroblasts from AERD and aspirin-tolerant subjects but had no effect on cyclooxygenase-2, EP4, and microsomal PGE synthase 1 (mPGES-1) mRNA levels.